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Quick Methods: Structure-Activity Relationships and Short-Term Bioassay
Published in Samuel C. Morris, 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.
Free Radical Damage and Lipid Peroxidation
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Richard O. Recknagel, Eric A. Glende, Robert S. Britton
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:
Different kinds of infertility, possible reasons for infertility
Published in Elisabeth Hildt, Dietmar Mieth, In Vitro Fertilisation in the 1990s, 2018
Hans-Rudolf Tinneberg, Ulrich Göhring
Meanwhile increasing evidence suggests that halogenated hydrocarbons such as PCBs and PCDFs have an adverse effect on the reproductive system As demonstrated in table 1 environmental pollutants can also have hormone-like effects. Of major concern are substances that have an estrogenic effect. As it could be demonstrated in fish, in sexual differentiation there is a period that is sensitive to xenoestrogen compounds as could be shown by the appearance of female xenotypic characteristics (oviduct) in the gonad of the genetic male carp (Gemeno et al. 1996). Along these lines it is surprising to note that in Denmark a change in male-female ratio among newborn infants has been described which was attributed to possible environmental or other agents with toxic influence on the male reproductive system that might have led to the low male-female ratio (Möller 1996). In a Spanish study of risk factors for cryptorchidism it was concluded that an association between exposure to xenobiotics with hormone disruptive activity and increased risk of cryptorchidism was possible. So far, studies of risk factors for cryptorchidism have rarely analysed the role of overexposure during pregnancy to substances with endocrine disruptive activity (Garcia-Rodriguez 1996). A list of so-called endocrine disruptures with estrogenic activity is given below.
A review of the effects of the anesthetic gas nitrous oxide on the immune system; a starting point for future experiences
Published in Immunopharmacology and Immunotoxicology, 2020
Monireh Mohsenzadegan, Masoumeh Kourosh arami, Mojgan Oshaghi, Shahnam Sedigh Maroufi
As mentioned before, N2O is one of the anesthetic agents that are used extensively in operating rooms, and in addition to the patient, operating room staff and physicians are constantly exposed to this gas. Wrońska-Nofer et al. assessed oxidative stress and DNA damage in leukocytes in relation to the level of exposure to N2O and halogenated hydrocarbons. They reported that occupational exposure to N2O is associated with augmented oxidative DNA damage and the level of exposure in this context plays an essential role [41]. Bargellini et al. conducted a cross-sectional study to evaluate the association between occupational exposure to low levels of N2O and isoflurane with lymphocyte changes in 51 anesthetists from different services of anesthesiology and reanimation departments. They found that CD3+ T cells were reduced and NK cells (CD16+/CD3+) were increased in anesthetists as compared to non-exposed physicians. The reduction of the percentage of total T cells correlated with the diminution of circulating T helper cells. They did not observe any changes in other lymphocyte subpopulations or cytotoxic activity of NK cells [5].
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.