Free Radical Damage and Lipid Peroxidation
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
The hepatotoxicity of halogenated hydrocarbons in its general aspects will be discussed elsewhere in this book. Comments here will be confined to CCl4 and CBrCl3. CCl4 and its closely related congener CBrCl3 are classic examples of toxigenic halogenomethanes. CBrCl3 is considerably more toxic than CCl4, a fact that depends on a lower bond dissociation energy for the C-Br bond relative to the C-Cl bond (Koch et al., 1974). In the case of CCl4, it is well known that its toxicity depends on reductive dehalogenation by a specific cytochrome P450 isozyme (see Recknagel and Glende, 1973; Recknagel et al., 1977, Brattin et al., 1985, and Recknagel et al., 1989, for reviews on CCl4 hepatotoxicity). Recently it has been shown that isolated rat liver mitochondria also carry out reductive dehalogenation of CCl4 (Tomasi et al., 1987). The one-electron reduction generates trichloromethyl radical:
Quick Methods: Structure-Activity Relationships and Short-Term Bioassay
Samuel C. Morris in Cancer Risk Assessment, 2020
Different salmonella tester strains are specific for a particular mutagenic action, and therefore to a specific class of mutagenic agents. Some classes of chemicals do not respond at all in the Ames test, although they have been shown to be mutagenic in other test systems or in humans. These include halogenated hydrocarbons and metals. A recent analysis by the International Program on Chemical Safety identified eight organics (Table 10-4), known to be human or animal carcinogens, which tested negative in the Ames test (Ashby et al., 1985). Some materials are difficult to test (i.e., gases) and the assay is made on extracts rather than the original material.
Organic Chemicals
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Among the halogenated hydrocarbons are several other industrially important agents used as solvents, chemical intermediates, and consumer products. Many are powerful liver and kidney toxic compounds. Some are carcinogens. Limited space prevents a detailed discussion of these here (Table 5.6). Most textbooks on chemistry, however, provide ample information about halogenated hydrocarbons.
Multi-Organ System Injury from Inhalant Abuse
Published in Prehospital Emergency Care, 2019
H. Evan Dingle, Saralyn R. Williams
Hydrocarbons are organic compounds composed of hydrogen and carbons atoms. When inhaled, hydrocarbons produce a euphoric effect. One subset, halogenated hydrocarbons, contains additional halogen elements such as chloride or fluoride. Volatile halogenated hydrocarbons are known to cause multisystem toxicity from both accidental and intentional inhalation (2). They are frequently abused due to their euphoric effects, low cost, and accessibility as they are found in many household products (2). Inhalant abuse has gained popularity and is particularly common among the adolescent and teenage population. The Monitoring the Future study demonstrated a decline in use among combined 8th, 10th, and 12th graders in 2015–2016; however, 2017 showed a significant increase in use by 8th graders. This study also noted that relatively low proportions of 8th and 10th graders believe there is “great risk” in using an inhalant once or twice (1).
Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety
Published in Cutaneous and Ocular Toxicology, 2018
Jessica C. Graham, Nathan Wilt, Gertrude-Emilia Costin, Caren Villano, Jackie Bader, Lindsay Krawiec, Elizabeth Sly, Janet Gould
An effort was made to understand the irritation potential of the chemical structural groups examined in this work (Table 3). While the test item data set is relatively small, generalizations can be made from the compounds which are well-represented. Salt forms are frequently utilized and changed during the pharmaceutical development process for ease of isolation and purification of solid PCs, and are expected to impact a PC’s skin and eye irritation potential. While salts with greater hydrogen donor potential may be considered obvious corrosives/irritants, other salts do not follow such rules and would need to be examined on an individual basis (data not shown). The studies on halogenated heterocycles and halogenated hydrocarbons showed low skin and eye irritation potential and were generally concordant with the in vivo studies. Nitro compounds also demonstrated low irritation potential in these studies. However, both chemical groups have potential to cause sensitization and/or mutagenicity, respectively (data not shown), indicating that other toxicity endpoints cannot necessarily predict irritation. Conversely, one chemical structural group (boronic acids) was under-predicted in the BCOP studies compared to the in vivo studies, indicating that the eye irritation potential for PC-O and V (a boronate ester) should be further investigated.
Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Xiaole Chen, Min Gao, Rongchao Jian, Weiqian David Hong, Xiaowen Tang, Yuling Li, Denggao Zhao, Kun Zhang, Wenhua Chen, Xi Zheng, Zhaojun Sheng, Panpan Wu
Hexamethylphosphoric triamide (HMPA, 353 μL, 2 mmol) was added to a solution of compound 3 (1 g, 5.1 mmol) in dry THF (60 ml) under N2 atmosphere. Next, n-BuLi (2.44 ml, 6.12 mmol) was added slowly to the mixture at −40 °C and stirred at this temperature for 10 min. Then the mixture was allowed to heat to −10 °C, and various halogenated hydrocarbons (5.5 mmol) were added dropwise. The mixture was stirred at room temperature overnight. THF in the reaction mixture was removed under reduced pressure, and the residue was redissolved in EtOAc. The organic solution was washed with 1 M HCl solution and saturated brine, then dried over MgSO4 and evaporated. The crude product was chromatographed (PE/EtOAc = 15/1 to 5/1) to supply pure compound 4–17 (20%∼60%).
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