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Toxicology
Published in W. David Yates, Safety Professional’s, 2015
Other classifications of chemicals or toxins include carcinogens, co-carcinogens, epigenetic, genotoxic, mutagen, clastogen, and teratogen, which are described in the following. Carcinogen: Any substance or agent known to cause cancer. Carcinogens do not adhere to the dose–response curve.Co-carcinogen: These agents, when applied immediately prior to or with a genotoxic carcinogen, enhance the oncogenic (cancerous) effect of the agent.Epigenetic: Changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence.Genotoxic: These materials are known to be potentially mutagenic and carcinogenic in nature. They act directly by altering the DNA.Mutagen: A physical or chemical agent that changes the genetic material (usually DNA) of an organism and thus increases the frequency of mutagens above the natural background level.Teratogens: Any agent that can disturb the development of an embryo or fetus.
Technical Approach to Human Health Endangerment Assessment
Published in Kofi Asante-Duah, Management of Contaminated Site Problems, 2019
Carcinogenesis is the process by which normal tissue becomes cancerous—i.e., the production of cancer, most likely via a series of steps—viz., initiation, promotion, and progression; the carcinogenic event modifies the genome and/or other molecular control mechanisms of the target cells, giving rise to a population of altered cells. An important issue in chemical carcinogenesis relates to the concepts of “initiators” and “promoters.” An initiator is a chemical/substance or agent capable of starting but not necessarily completing the process of producing an abnormal uncontrolled growth of tissue, usually by altering a cell’s genetic material; thus, initiated cells may or may not be transformed into tumors. A promoter is defined as an agent that results in an increase in cancer induction when it is administered at some time after a receptor has been exposed to an initiator; thus, this represents an agent that is not carcinogenic in itself, but when administered after an initiator of carcinogenesis, serves to dramatically potentiate the effect of a low dose of a carcinogen—by stimulating the clonal expansion of the initiated cell to produce a neoplasm. Further yet, a co-carcinogen is an agent that is not carcinogenic on its own, but enhances the activity of another agent that is carcinogenic when administered together with the carcinogen; it is noteworthy that a co-carcinogen differs from a promoter only in that the former is administered at the same time as the initiator. It is believed that initiators, co-carcinogens, and promoters do not usually induce tumors when administered separately. Indeed, it has become apparent that a series of developmental stages is required for carcinogenesis (OSTP, 1985). Many chemical carcinogens are believed to be complete carcinogens—i.e., chemicals that are capable of inducing tumors in animals or humans without supplemental exposure to other agents; thus, these chemicals function as both initiators and promoters. Generally speaking, the term “complete” refers to the three stages of carcinogenesis (namely: initiation, promotion, and progression) that need to be present in order to induce a cancer. It should be acknowledged, however, that promoters themselves are usually not necessarily carcinogens; these may include dietary fat, alcohols, saccharin, halogenated solvents, and estrogen. Even so, most regulatory agencies in many different jurisdictions do not usually distinguish between initiators and promoters, especially because it is often very difficult to confirm whether a given chemical acts by promotion alone, etc. (OSHA, 1980; OSTP, 1985; USEPA, 1984a,c).
No clear concerns related to health risks in the European population with low inorganic arsenic exposure (overview)
Published in Human and Ecological Risk Assessment: An International Journal, 2023
Zdenka Šlejkovec, Tine Bizjak, Milena Horvat, Ingrid Falnoga
Excess lifetime cancer risk (for lung or lung and bladder cancer) estimated according to currently (still) proposed linear non-threshold approaches (ECHA 2013, cancer slopes) does show an increased risk for adults in the range of 1–3 × 10−4 (Table 3). However as commented above several research groups recently advocate for the use of the nonlinear approach (Rhomberg et al. 2011; Lynch et al. 2017a; Boffeta and Borron 2019; Lamm et al. 2018, 2021; Tsuji et al. 2019; Ahn et al. 2020; Shao et al. 2021). In addition to uncertainties related to the dose response of arsenic-caused cancer at low exposure levels, there are additional uncertainties, specific to the use of HBM data. These include uncertainty related to the representativeness of populations and applicability of epidemiological data, overestimation of iAs due to the widespread presence of DMA in food, analytical challenges related to the speciation of As species in urine, inter-individual differences (gender, ethnicity, smoking, undefined exposures to co-carcinogen, chronic diseases, etc.). Accordingly, the estimated cancer risk assessment is of poor relevance, and the prediction is overestimated.
Application of the adverse outcome pathway (AOP) approach to inform mode of action (MOA): A case study with inorganic arsenic
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Harvey J. Clewell, Janice W. Yager, Tracy B. Greene, P. Robinan Gentry
A diagram of the proposed MOA for iAs cancer and non-cancer effects is illustrated in Figure 3. While disruption of oxidative stress response signaling is a key element of this MOA, oxidative stress itself is not considered a necessary factor in the production of cancer or non-cancer effects mediated by iAs. Generation of oxidative stress alone cannot explain the well-demonstrated ability of iAs to serve as a co-mutagen and co-carcinogen. In the present MOA, the co-mutagenicity and co-carcinogenicity of iAs may be related to inhibition of DNA repair.