• Title/Summary/Keyword: Threshold of toxicological concern

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Thresholds of Genotoxic and Non-Genotoxic Carcinogens

  • Nohmi, Takehiko
    • Toxicological Research
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    • v.34 no.4
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    • pp.281-290
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    • 2018
  • Exposure to chemical agents is an inevitable consequence of modern society; some of these agents are hazardous to human health. The effects of chemical carcinogens are of great concern in many countries, and international organizations, such as the World Health Organization, have established guidelines for the regulation of these chemicals. Carcinogens are currently categorized into two classes, genotoxic and non-genotoxic carcinogens, which are subject to different regulatory policies. Genotoxic carcinogens are chemicals that exert carcinogenicity via the induction of mutations. Owing to their DNA interaction properties, there is thought to be no safe exposure threshold or dose. Genotoxic carcinogens are regulated under the assumption that they pose a cancer risk for humans, even at very low doses. In contrast, non-genotoxic carcinogens, which induce cancer through mechanisms other than mutations, such as hormonal effects, cytotoxicity, cell proliferation, or epigenetic changes, are thought to have a safe exposure threshold or dose; thus, their use in society is permitted unless the exposure or intake level would exceed the threshold. Genotoxicity assays are an important method to distinguish the two classes of carcinogens. However, some carcinogens have negative results in in vitro bacterial mutation assays, but yield positive results in the in vivo transgenic rodent gene mutation assay. Non-DNA damage, such as spindle poison or topoisomerase inhibition, often leads to positive results in cytogenetic genotoxicity assays such as the chromosome aberration assay or the micronucleus assay. Therefore, mechanistic considerations of tumor induction, based on the results of the genotoxicity assays, are necessary to distinguish genotoxic and non-genotoxic carcinogens. In this review, the concept of threshold of toxicological concern is introduced and the potential risk from multiple exposures to low doses of genotoxic carcinogens is also discussed.

Cross-media Approaches to Risk Management of Environmental Pollution in Korea (한국에서의 환경오염에 의한 위해성관리의 종합적 접근방법)

  • Chong, Yong
    • Environmental Analysis Health and Toxicology
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    • v.4 no.1_2
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    • pp.55-65
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    • 1989
  • Nevertheless the serious environmental pollution in Korea has been discussed in concern with health effect, the significant effect are not determined easily. Toxicological method has been used to establish safe levels of exposure for environmental pollutants to have threshold health effect below which significant effects are unlikely to occur. However the conventional method cannot to establish safe levels of exposure for non-threshold pollutants have been used to express comprehensive pollution degree, not in detailed toxic effects. Acceptable exposure or risk levels are decides by policymakers who consider descriptions and estimates of risks together with social and economic benefits. This paper focuses on the concept development of risk assessment and describes some risks of environmental pollution based on the surveyed date in Korea. The current concepts of risk assessment in policy descisions can be explored and areas for possible improvement, given current scientific knowledge are identified. The experience of foreign countries can provide a realistic basis for evaluating the existing data of environmental pollutants. To improve the environmental quality, risk regulation should be managed as soon as possible in Korea.

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Establishment of Acceptable Daily Intakes (ADIs) and Risk Assessment for Ephedrine, Menichlopholan, Anacolin, and Etisazole Hydrochloride

  • Min Ji Kim;Ji Young Kim;Jang Duck Choi;Guiim Moon
    • Korean Journal of Environmental Agriculture
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    • v.41 no.4
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    • pp.261-275
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    • 2022
  • BACKGROUND: Prior to implementing a positive list system (PLS), there is a need to establish acceptable daily intake (ADI) and maximum residue limit (MRL) for veterinary drugs that have been approved a few decades ago in South Korea. On top of that, chronic dietary exposure assessment of veterinary drug residues should be performed to determine whether the use of these veterinary drugs would cause health concerns or not. METHODS AND RESULTS: To establish the ADI, the relevant toxicological data were collected from evaluation reports issued by international organizations. A slightly modified global estimate of chronic dietary exposure (GECDE) model was employed in the exposure assessment owing to the limited residual data. Therefore, only the ADI of ephedrine was established due to insufficient data for the other veterinary drugs. Thus, instead of ADI, the threshold of toxicological concern (TTC) value was used for the other drugs. Lastly, the hazard index (HI) was calculated, except for etizazole hydrochloride, due to the potential of mutagenicity. CONCLUSION(S): The HI values of ephedrine, menichlopholan, and anacolin were found to be as high as 6.4%, suggesting that chronic dietary exposure to the residues from these uses was unlikely to be a public health concern. Further research for exposure assessment of veterinary drug residues should be performed using up-todate Korean national health and nutrition examination survey (KNHANES) food consumption data. In addition, all relevant available data sources should be utilized for identifying the potentials of toxicity.