• 제목/요약/키워드: Carcinogenic Potency

검색결과 18건 처리시간 0.027초

위해성 평가 및 관리에 있어서 발암물질의 인체발암능력 평가 (Estimation of Human Carcinogenic Potency (HCP) of Carcinogens in Risk Assessment and Management.)

  • 이병무;김대영;김세기;김근종
    • 한국환경성돌연변이발암원학회지
    • /
    • 제19권1호
    • /
    • pp.39-45
    • /
    • 1999
  • Human Carcinogenic Potency (HCP) can be estimated based on human daily exposure dose to carcinogen (Dh), body weight (Wh), 10% tumorigenic dose (TD10), and slope factor at TD10 (Q10) from 2-yr bioassay data. This approach is more relevant to humans generally exposed to low doses of carcinogens and can reduce more of extrapolation errors from high dose in animal experiments to low dose in humans than HERP (human exposure dose/rodent potency dose) proposed by Ames et al. (Science, 236, 271-280, 1987). TD50 and HERP have been routinely used to compare rodent carcinogenic potency and human carcinogenic potency, but those approaches have had limitations in extrapolation of high dose to low dose in humans. The advantages of HCP are to estimate human exposure dose (Dh) by human monitoring instead of environmental monitoring, to consider slope factor (Q10) which reflects the tendency of curve at low dose, and to use TD10 which represents much lower dose thant TD50 or HERP. HCP will be a useful parameter for the estimation of human carcinogenic potency in risk assessment and management of carcinogens.

인체상피세포를 이용한 Vinyl acetate의 발암성 및 작용기전 (HIGH DOSE EXPOSURES OF VINYL ACETATE INDUCE NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE)

  • 조준현;김진수
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
    • /
    • 제33권5호
    • /
    • pp.437-444
    • /
    • 2007
  • Vinyl acetate has been widely used for the manufacture of polyvinyl alcohol emulsion, which is primary ingredient of adhesive, paints, textile, paperboard coatings, etc. Since these products are plentiful and frequently used around us, workers and consumers are at health risk. International Agency for Research on Cancer(IARC) classified vinyl acetate as group 2B(possibly carcinogenic to humans). Among the organs targeted, the oral cavity is the most vulnerable organ affected by the carcinogenic effects of vinyl acetate. Since the origin of most of oral cancer is derived from the epithelial cells, it is important to understand the carcinogenic potential of vinyl acetate in human epithelial cells. Thus, the present study has attempted to utilize the immortalized human epithelial cell model to assess the carcinogenic potency of this chemical and to understand the underlying mechanisms.

석유화학단지의 휘발성 유기화합물로 인한 인체 위해도 평가에 관한 연구 (A Study on the Health Risk Assessment of Volatile Organic Compounds in a Petrochemical Complex)

  • 이진홍;김윤신;류영태;유인석
    • 한국대기환경학회지
    • /
    • 제13권4호
    • /
    • pp.257-267
    • /
    • 1997
  • This study focuses on the health risk assessment of airborne volatile organic compounds (VOCs) in a petrochemical complex, with several emphases on a risk assessment method. The first emphasis is on the importance of hazard identification to determine the likely carcinogenic potential of a VOC. Without considering this type of information, a direct comparison of the carcinogenic risks of two pollutants is meaningless. Therefore, wer suggest that this type of information be prepared and be listed with the estimate of cancer risk in parallel. The second emphasis is on the selection of a better dose-response model to estimate unit risk or cancer potency factor of a carcinogenic VOC. Finally, probilistic risk assessment method is discussed and recommended to use within a comparison of conventional point-estimate method. A health risk assessment has also been carried out. For non-carcinogenic risk, even the highest hazard index for carbon tetrachloride is estimated to be less than 1 with the other VOCs less than 0.03. However, the lifetime cancer risk from the inhalation of airborne VOCs is estimated to be about $2.6 \times 10^{-4}$ which is higher than the risk standard of $10^{-6}$ or even $10^{-5}$. Therefore, the investigation into domestic petrochemical complexes should be strengthened to obtain more fine long-term airborne VOC data.

  • PDF

N-nitroso-N-methylurea and N-nitroso-N-ethylurea Decrease in Nitric Oxide Production in Human Malignant Keratinocytes

  • Moon, Ki-Young
    • 대한의생명과학회지
    • /
    • 제24권1호
    • /
    • pp.50-54
    • /
    • 2018
  • N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), direct alkylating chemical mutagens and carcinogens, are shown to be the upregulators of cellular $NF-{\kappa}B$, regulating various genes that mediate tumorigenesis and carcinogenesis. Nitric oxide (NO), a toxic reactive radical gas, has been known to induce programmed cell death or apoptosis in various cells. Therefore, the assessment of NO production was examined to elucidate the possible contribution of NO release to the chemical carcinogenic potency of NMU and NEU in human skin cells. NMU and NEU did not alter the NO production, but they caused a significant downregulation of the NO generation on lipopolysaccharide (LPS)-induced NO production at concentrations ranging from $2{\sim}5{\mu}M$. The degree of downregulation of NO by NMU and NEU decreased up to 15% and 20%, respectively, compared to the control. These results demonstrate that the LPS-inducible keratinocytes NO synthase is involved in modulating carcinogenic potency by NMU and NEU, and the regulation of the cellular $NF-{\kappa}B$ activity by NMU and NEU is negatively correlated with the level of LPS-induced NO production in human skin cells. The findings of this study suggest the hypothesis that NMU and NEU-induced carcinogenesis may be associated with the downregulation of NO production, and the inducible NO may play an important role in NMU and NEU-induced carcinogenicity in human epidermal keratinocytes.

DIETARY RISK ASSESSMENT FOR POLYCYCLIC AROMATIC HYDROCARBONS IN FOOD

  • Hyomin LEE;Eunkyung YOON;Yoonho CHOI;Gunyoung LEE;Yonsook JO;Kisung KWON;Soyoung CHUNG;Myungchul KIM;Jisun YANG
    • 한국독성학회:학술대회논문집
    • /
    • 한국독성학회 2002년도 Current Trends in Toxicological Sciences
    • /
    • pp.136-136
    • /
    • 2002
  • Polycyclic aromatic hydrocarbons(PAHs) vary in their carcinogenic potencies. The more potent PAHs carcinogens are 3-methylcholantheren and 7, 12- dimethyl benzo(a)anthracene, while dibenzo(a, c)anthracene has very little carcinogenic activity. Risk assessment of chemical mixture containing various congeners which toxic potency are each different, are conducted using toxic equivalency factors(TEFs).(omitted)

  • PDF

대기중 복합물질의 돌연변이원성과 인체 위해도 (Health Risk of Airborne Complex Mixtures Based on their Mutagenicity)

  • 박성은;정용
    • 한국대기환경학회지
    • /
    • 제12권3호
    • /
    • pp.269-278
    • /
    • 1996
  • Airborne suspended particulates were collected by an Andersen high volume air sampler in a traffic area of Seoul from September 1990 to August 1991. Origanic matter extracted from particulates, their fractions, namely acidic, basic, neutral and carcinogenic subfractions (PAHs, nitroarenes) in neutral fractions were assayed for mutagenicity on TA98, TA100 and TA98NR deficient Salmonella strains, use of the pre-incubation method. The relative contribution to total mutanenicity of organic matters was highest in neutral fraction and was lowest in basic fraction. Among subfractions, that of neutral fraction was higher nitroarenes subfraction compared to PAHs subfraction. While the carcinogenic effect of benzo[a]pyrene was calculated as 0.96 persons/million persons based on unit risk estimates by extrapolation method, life time excess cancer risk estimate of EOM, neutral, PAH fraction based on their mutagenicity was calculated as 52, 42, 3.8 persons/million persons, respectively. These findings indicate that the mutagenic hazard of the partciculate, air organic complex mixture, may be dependent upon the mutagen composition in the particulate and interactions each of them. Therfore, health risk from air organic complex mixtures based on mutagenicity might be useful indicator for evaluation of actual risk.

  • PDF

Quantitative and Qualitative Extrapolation of Carcinogenesis Between Species

  • Gold Lois Swirsky;Manley Neela B.;Ames Bruce N.
    • 대한예방의학회:학술대회논문집
    • /
    • 대한예방의학회 1994년도 교수 연수회(환경)
    • /
    • pp.431-438
    • /
    • 1994
  • As currently conducted, standard rodent bioassays do not provide sufficient information to assess carcinogenic risk to humans at doses thousands of times below the maximum tolerated dose. Recent analyses indicate that measures of carcinogenic potency from these tests are restricted to a narrow range about the maximum tolerated dose and that information on shape of the dose-response is limited in experiments with only two doses and a control. Extrapolation from high to low doses should be based on an understanding of the mechanisms of carcinogenesis. We have postulated that administration of the maximum tolerated dose can increase mitogenesis which, in turn. increases rates of mutagenesis and, thus, carcinogenesis. The animal data are consistent with this mechanism, because about half of all chemicals tested are indeed rodent carcinogens, and about 40% of the positives are not detectably mutagenic. Thus, at low doses where cell killing does not occur, the hazards to humans of rodent carcinogens may be much lower than commonly assumed. In contrast, for high-dose exposures in the workplace, assessment of hazard requires comparatively little extrapolation. Nevertheless. permitted workplace exposures are sometimes close to the tumorigenic dose-rate in animal tests. Regulatory policy to prevent human cancer has primarily addressed synthetic chemicals, yet similar proportions of natural chemicals and synthetic chemicals test positive in rodent studies as expected from an understanding of toxicological defenses, and the vast proportion of human exposures are to natural chemicals. Thus, human exposures to rodent carcinogens are common. The natural chemicals are the control to evaluate regulatory strategies, and the possible hazards from synthetic chemicals should be compared to the possible hazards from natural chemicals. Qualitative extrapolation of the carcinogenic response between species has been investigated by comparing two closely related species: rats and mice. Overall predictive values provide moderate confidence in interspecies extrapolation; however, knowing that a chemical is positive at any site in one species gives only about a 50% chance that it will be positive at the same site in the other species.

  • PDF

An Examination of Variation in Risk Assessment Practices in Relation to Assessors' Goals: American and International Practices

  • Park, Lorenz R. mberg
    • Toxicological Research
    • /
    • 제17권
    • /
    • pp.219-225
    • /
    • 2001
  • The basic structure for assessment of potential health risks from environmental chemicals is widely agreed upon, but many of the details of risk assessment procedures differ among practitioners. Government regulatory agencies typically have guidelines or standard procedures for their risk assessments, established to ensure consistency and comparability, to set standards for adequacy, and to embody underlying tenets. In setting and updating such guidelines, each agency takes into account not only the prevailing thinking about appropriate procedures, but also its own goals and responsibilities and the precedents it has set for itself in past analyses. This results in variations in methods, and consequently in characterization of risks, among regulatory assessments, even when they are based on the same data. As a result, adopting existing assessments from a variety of regulatory bodies needs to be done with caution. This paper examines some of the variants in risk assessment approaches among American federal regulatory agencies and relates them to the variations in regulatory responsibilities of those groups. Comparisons to international practices are also drawn. The impact on development of world-wide risk standards is discussed.

  • PDF

산업계 배출수에서 포름알데히드의 배출허용기준 설정방안 고찰 (A Study on the Determination of Formaldehyde Effluent Limitation in the Industrial Wastewater)

  • 정동환;신진수;신기식;김재훈;김용석;류덕희
    • 환경영향평가
    • /
    • 제22권3호
    • /
    • pp.203-217
    • /
    • 2013
  • This study looked at how to establish effluent limitation standards for formaldehyde, a toxic chemical widely used in industries. To this end, we reviewed Water Quality Based Effluent Limitation (WQBEL), Technology Based Effluent Limitation (TBEL), and water quality criteria for protection of human health and aquatic organism. Based on the results, we estimated formaldehyde effluent limitation standards appropriate to control water quality of industrial wastewater in Korea. However, this study has limits due to the lack of some data necessary in estimating formaldehyde effluent limitation. For example, although water quality criteria based on non-carcinogenic properties of formaldehyde were calculated, those based on carcinogenic properties were not be able to estimate because of the absence of applicable cancer potency factor q1. Without applicable factor, we calculated water quality standards for formaldehyde based on water quality criteria of advanced countries including the United States, while with no water quality standard we referred to applicable drinking water quality standards of other countries. For eco-toxicity based on water quality criteria, proper figures could not be calculated since there have been few reliable data.

Differential Effects of Nongenotoxic and Genotoxic Carcinogens on the Preneoplastic Lesions in the gat Liver

  • Kim, Dae-Joong;Lee, Kook-Kyung;Hong, Jin-Tae
    • Archives of Pharmacal Research
    • /
    • 제21권4호
    • /
    • pp.363-369
    • /
    • 1998
  • Glutathione S-transferase placental form (GST-P) positive foci development and its expression in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate (CF), and genotoxic carcinogen 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) were investigated as a measure of carcinogenic potential of these chemicals. Male F344 rats were initially given a single intraperitioneal injection of diethyinitrosamine (200 mg/kg), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CF or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed at 8 weeks or 52 weeks, and liver tissues were examined for immunohistochemical staining of GST-P positive foci. The numbers (No./$cm^2$) and areas ($mm^2$/ $cm^2$) of GST-P positive foci were increased by IQ or PB, but were decreased by CF compare to the control. Consistent with the development of GST-P positive foci, a time-related increase in the expression of GST-P mRNA was found in the rats treated with IQ, whereas CF decreased it. The incidence of hepatocellular carcinoma at 52 weeks was increased by all three chemicals. These results show that PB and IQ induced GST-P positive foci, but the peroxisome proliferator CF did not, which suggest that the prediction of carcinogenic potency based on the development of prenoplastic foci may cause false negative in a particular category compounds like peroxisome proliferators.

  • PDF