WorldWideScience

Sample records for human carcinogenic risk

  1. Human exposure to dioxins through the diet in Catalonia, Spain: carcinogenic and non-carcinogenic risk.

    Science.gov (United States)

    Llobet, Juan M; Domingo, Jose L; Bocio, Ana; Casas, Conrad; Teixidó, Angel; Müller, Lutz

    2003-03-01

    The main objectives of this study were to estimate the dietary intake of dioxins by the population of Catalonia, Spain, to determine which food groups showed the greatest contribution to this intake, and to assess the health risks potentially associated with the dietary dioxin intake. From June to August 2000, food samples were randomly acquired in seven cities of Catalonia. Dioxin concentrations were determined in 108 samples belonging to the following groups: vegetables, fruits, pulses, cereals, fish and shellfish, meats and meat products, eggs, milk and dairy products, and oils and fats. Estimates of average daily food consumption were obtained from recent studies. Total dietary intake of dioxins for the general population of Catalonia was estimated to be 95.4 pg WHO-TEQ/day (78.4 pg I-TEQ/day), with fish and shellfish (31%), diary products (25%), cereals (14%) and meat (13%) showing the greatest percentages of contribution to dioxin intake. The contribution of all the rest of food groups to the total dietary intake was under 20%. The non-carcinogenic risk index of dioxin intake through the diet was in the range 0.34-1.36, while the carcinogenic risk level was 1,360 excess cancer over a lifetime of 70 years. Our results corroborate the decreasing tendency in dietary intake of dioxins found in recent studies (2000-2001) from various countries.

  2. Human health risk due to consumption of vegetables contaminated with carcinogenic polycyclic aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Sardar [Chinese Academy of Sciences, Xiamen (China). Inst. of Urban Environment; Peshawar Univ. (Pakistan). Dept. of Environmental Science; Cao, Qing [Chinese Academy of Sciences, Beijing (China). Research Center for Eco-Environemntal Sciences

    2012-02-15

    Polycyclic aromatic hydrocarbons (PAH) are persistent, toxic, and carcinogenic contaminants present in soil ecosystem globally. These pollutants are gradually accumulating in wastewater-irrigated soils and lead to the contamination of vegetables. Food chain contamination with PAH is considered as one of the major pathways for human exposure. This study was aimed to investigate the concentrations of PAH in soils and vegetables collected from wastewater-irrigated fields from metropolitan areas of Beijing, China. Origin of PAH, daily intake, and health risks of PAH through consumption of contaminated vegetables were studied. Soil samples were collected from the upper horizon (0-20 cm) of both wastewater-irrigated and reference sites and sieved (<2 mm mesh) and then followed by freeze-drying at -50 C and 123 {+-} 2 Pa. Standing vegetables were also collected from the same sites used for soil sampling and divided into roots and shoots, thoroughly washed with deionized water, and freeze-dried. PAH were extracted using the Soxhlet method with 200 mL DCM for 24 h, and the extracts were cleaned with silica adsorption chromatography prepared with silica gel, alumina, and capped with anhydrous sodium. The final concentrated extracts (soil and vegetable) were analyzed using gas chromatography-mass spectrometry (Agilent 6890). Bioaccumulation factors, daily intake of PAH, and carcinogenicity of PAH were calculated by different statistical equations. Results indicate that the soils and grown vegetables were contaminated with all possible carcinogenic PAH (declared by USEPA 2002) except indeno[1,2,3-c,d]pyrene. The highest concentration (242.9 {mu}g kg{sup -1}) was found for benzo(k)fluoranthene (BkF), while lowest (79.12 {mu}g kg{sup -1}) for benzo[a]pyrene (BaP). The emission sources of PAH were both pyrogenic and petrogenic in nature. However, the total concentrations of PAH were lower than the permissible limits set by different countries like Canada, Denmark and Germany

  3. Formation and Human Risk of Carcinogenic Heterocyclic Amines Formed from Natural Precursors in Meat

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M G; Felton, J S

    2004-11-22

    A group of heterocyclic amines that are mutagens and rodent carcinogens form when meat is cooked to medium and well-done states. The precursors of these compounds are natural meat components: creatinine, amino acids and sugars. Defined model systems of dry-heated precursors mimic the amounts and proportions of heterocyclic amines found in meat. Results from model systems and cooking experiments suggest ways to reduce their formation and, thus, to reduce human intake. Human cancer epidemiology studies related to consumption of well-done meat products are listed and compared.

  4. Acrylonitrile: a suspected human carcinogen.

    Science.gov (United States)

    Koerselman, W; van der Graaf, M

    1984-01-01

    The literature on carcinogenicity of acrylonitrile (an important intermediate in the chemical industry) is reviewed. The three main conclusions are: (1) Acrylonitrile has genotoxic effects in various tests in microorganisms and in mammal cells. (2) Chronic exposure to acrylonitrile causes tumours in rats. (3) Results of epidemiological studies indicate that acrylonitrile may be a human carcinogen. From this it is clear that acrylonitrile is very probably carcinogenic to humans. Therefore the authors plead for a reduction of acrylonitrile standards to the lowest practicable limit.

  5. Glyphosate and Carcinogenicity Risk

    OpenAIRE

    Ötegen, Volkan Recai; Akbaba, Muhsin; Nazlıcan, Ersin

    2015-01-01

    IARC Glyphosate's IIA classification is still controversial, because dosages of this effect is not specified and also numerous studies show the opposite. However, the results must be noted by scientific institutions and public health authorities and risk assessment must be made considering doses and real-life conditions.

  6. [The implementation of polymerase chain reaction technique: the real time to reveal and differentiate the viruses of human papilloma of high carcinogenic risk].

    Science.gov (United States)

    Andosova, L D; Kontorshchikova, K N; Blatova, O L; Kudel'kina, S Iu; Kuznetsova, I A; Belov, A V; Baĭkova, R A

    2011-07-01

    The polymerase chain reaction technique was applied in "real time" format to evaluate the occurrence rate and infection ratio of various genotypes of human papilloma of high carcinogenic risk in virus-positive women and contact persons. The examination sampling consisted of 738 women aged of 17-50 years. The examination results permitted to establish high percentage of infection of 546 patients (74%) by carcinogenic papilloma viruses. The analysis of detection rate of various genotypes of human papilloma of high carcinogenic risk established that the 56th and 16th types of high carcinogenic risk are revealed more often than others--in 33% and 15.4% correspondingly. In males, first place in occurrence rate is for those types of virus of human papilloma: the 56th n = 10 (33.3%), 16th n = 3 (10%), 45th n = 3 (10%), 51th n = 3 (10%). The rest of genotypes are detected in 3-7% cases.

  7. Genotoxicity and carcinogenicity risk of carbon nanotubes.

    Science.gov (United States)

    Toyokuni, Shinya

    2013-12-01

    Novel materials are often commercialized without a complete assessment of the risks they pose to human health because such assessments are costly and time-consuming; additionally, sometimes the methodology needed for such an assessment does not exist. Carbon nanotubes have the potential for widespread application in engineering, materials science and medicine. However, due to the needle-like shape and high durability of multiwalled carbon nanotubes (MWCNTs), concerns have been raised that they may induce asbestos-like pathogenicity when inhaled. Indeed, experiments in rodents supported this hypothesis. Notably, the genetic alterations in MWCNT-induced rat malignant mesothelioma were similar to those induced by asbestos. Single-walled CNTs (SWCNTs) cause mitotic disturbances in cultured cells, but thus far, there has been no report that SWCNTs are carcinogenic. This review summarizes the recent noteworthy publications on the genotoxicity and carcinogenicity of CNTs and explains the possible molecular mechanisms responsible for this carcinogenicity. The nanoscale size and needle-like rigid structure of CNTs appear to be associated with their pathogenicity in mammalian cells, where carbon atoms are major components in the backbone of many biomolecules. Publishing adverse events associated with novel materials is critically important for alerting people exposed to such materials. CNTs still have a bright future with superb economic and medical merits. However, appropriate regulation of the production, distribution and secondary manufacturing processes is required, at least to protect the workers.

  8. Laser diagnostics of native cervix dabs with human papilloma virus in high carcinogenic risk

    Science.gov (United States)

    Peresunko, O. P.; Karpenko, Ju. G.; Burkovets, D. N.; Ivashko, P. V.; Nikorych, A. V.; Yermolenko, S. B.; Gruia, Ion; Gruia, M. J.

    2015-11-01

    The results of experimental studies of coordinate distributions of Mueller matrix elements of the following types of cervical scraping tissue are presented: rate- low-grade - highly differentiated dysplasia (CIN1-CIN3) - adenocarcinoma of high, medium and low levels of differentiation (G1-G3). The rationale for the choice of statistical points 1-4 orders polarized coherent radiation field, transformed as a result of interaction with the oncologic modified biological layers "epithelium-stroma" as a quantitative criterion of polarimetric optical differentiation state of human biological tissues are shown here. The analysis of the obtained Mueller matrix elements and statistical correlation methods, the systematized by types studied tissues is accomplished. The results of research images of Mueller matrix elements m34 for this type of pathology as low-grade dysplasia (CIN2), the results of its statistical and correlation analysis are presented.

  9. [Leather azo dyes: mutagenic and carcinogenic risks].

    Science.gov (United States)

    Clonfero, E; Venier, P; Granella, M; Levis, A G

    1990-01-01

    The paper reviews the carcinogenicity and mutagenicity data on azo dyes used in the leather industry. Two water soluble benzidine-based dyes were classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer (IARC). No other dyes have been evaluated by the IARC. Of the 48 azo dyes assayed in the Salmonella/microsome test, 20 gave positive results. Attention is drawn to the important role of the in vivo metabolism of azo compounds, which includes a preliminary reduction of the azo bonds and subsequent release of the aromatic amines of the dye. A useful assay (Prival test) for evaluating the mutagenic properties of azo dyes involves a reductive step that permits the release of any genotoxic agents present in the compounds. A list of leather azo dyes is furnished that are considered as potentially harmful due to the presence of a carcinogenic aromatic amine (benzidine, p-aminobenzene and derivatives) in their formulae.

  10. RADON AND CARCINOGENIC RISK IN MOSCOW

    Directory of Open Access Journals (Sweden)

    S. M. Golovanev

    2015-01-01

    Full Text Available Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published values оf total population carcinogenic risk from chemical carcinogens.Results: it is shown that the 304 cases of lung cancer per year (1. 85 10-3 on average from 2006 to 2011 (21280diseases for 70 years in addition to background level induced by radon; the differences in average trends of all lungcancer incidence in the districts can exceed 25%.Conclusion. The potential of risk reduction by measures of mitigation radon concentration exceeds 5 times the cost efficiency to reduce emissions from vehicles and can reduce cancer incidence, on average 236 cases per year; population risk 16520 cases over 70 years or save not less than 2832 person-years of life per year. The annual effect of reducing losses from not-survival of 12 years as a result of radon-induced lung cancer deaths exceeds 14160000 dollars. The evaluating of the carcinogenic risk from radon in accordance with the definition of population risk increases the predictive evaluation of the effectiveness of preventive measures more than twice.

  11. Non-regulatory and cost-effectiveness control of carcinogenic hazard. The beginnings: a methodology for using animal data to decrease uncertainty in human risk of carcinogens released by energy technologies

    Energy Technology Data Exchange (ETDEWEB)

    Crouch, E.A.C.; Feller, J.; Fiering, M.B.; Hakanoglu, E.; Wilson, R.; Zeise, L.

    1982-09-01

    A logical cost effective procedure for assessing carcinogenic risk associated with emerging energy technologies is outlined. All chemicals are assumed to be carcinogenic with a potency that has to be measured. In this scheme a non-carcinogen is a chemical with zero potency. If the carcinogenic potency in animals has not been measured, it may be assumed from an a priori measure. Using estimates of potency, exposure, and an interspecies factor (which also accounts for uncertainties in extrapolating the animal data to man), an estimate of risk and the uncertainty associated with that estimate is made, together with upper bounds on the risk. If the upper bound is small the risk is negligible and can be ignored. If it is large, the exposure at the level proposed should not be permitted. However further information may be obtained which changes the risk estimate or lowers the uncertainty so that the upper bound on the risk is reduced. Notice that estimation of the uncertainty is as important as estimation of a best value of risk.

  12. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia H

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' fa

  13. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia H

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' fa

  14. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    NARCIS (Netherlands)

    Pearce, Neil E; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier A; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick|info:eu-repo/dai/nl/072910542; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans|info:eu-repo/dai/nl/074385224; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Kristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela C; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Seniori Constantini, Adele; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silvermann, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel|info:eu-repo/dai/nl/216532620; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia H

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups'

  15. Critical factors in assessing risk from exposure to nasal carcinogens.

    Science.gov (United States)

    Bogdanffy, M S; Mathison, B H; Kuykendall, J R; Harman, A E

    1997-10-31

    Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose-response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.

  16. Known and Probable Human Carcinogens

    Science.gov (United States)

    ... other does not necessarily mean there is a controversy, as one agency may not have evaluated it. ... to humans Acrylamide Adriamycin (doxorubicin) Androgenic (anabolic) steroids Art glass, glass containers, and press ware (manufacture of) ...

  17. Artificial sweeteners--do they bear a carcinogenic risk?

    Science.gov (United States)

    Weihrauch, M R; Diehl, V

    2004-10-01

    Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.

  18. DNA adducts in human tissues:biomarkers of exposure to carcinogens in tobacco smoke

    OpenAIRE

    Phillips, D.H.

    1996-01-01

    Tobacco smoking causes millions of cancer deaths annually. Tobacco smoke is a complex mixture of thousands of chemicals including many known animal carcinogens. Because many carcinogens from DNA adducts in target animal or human tissues, the detection of the formation of adducts using such methods as postlabeling, immunoassay, fluorescence spectroscopy, and mass spectrometry is a means of monitoring human exposure to tobacco carcinogens. Smokers are at increased risk of cancer in many organs,...

  19. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  20. The evolving definition of carcinogenic human papillomavirus

    Directory of Open Access Journals (Sweden)

    Castle Philip E

    2009-05-01

    Full Text Available Abstract Thirteen human papillomavirus (HPV genotypes have been judged to be carcinogenic or probably carcinogenic, and the cause of virtually all cervical cancer worldwide. Other HPV genotypes could possibly be involved. Although the inclusion of possibly carcinogenic HPV genotypes may hurt test specificity, it may indirectly increase the reassurance following a negative HPV test (i.e. the negative predictive value of an HPV test for cervical precancer and cancer. The future of cervical cancer screening in low-resource setting, however, may include once-in-a-lifetime, low-cost and rapid HPV testing. However, the tradeoff of more false positives for greater reassurance may not be acceptable if the local infrastructure cannot manage the screen positives. Now is the time for the community of scientists, doctors, and public health advocates to use the data presented at the 100th International Agency for Research on Cancer monograph meeting to rationally decide the target HPV genotypes for the next generation of HPV tests for use in high-resource and low-resource settings. The implications of including possibly HPV genotypes on HPV test performance, also for guidance on the use of these tests for cervical cancer prevention programs, are discussed.

  1. Prospective comparison of hybrid capture 2 and SPF₁₀-LiPA for carcinogenic human papillomavirus detection and risk prediction of cervical cancer: a population-based cohort study in China.

    Science.gov (United States)

    Dong, Li; Feng, Rui Mei; Zhang, Li; Xu, Xiao Qian; Zhao, Xue Lian; Wang, Margaret Zhuoer; Qiao, You Lin; Zhao, Fang Hui

    2017-09-01

    To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay and evaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer and precancers. Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I) cohort from 2005 to 2014 in Shanxi, China, SPF₁₀-line probe assay (LiPA) was performed in all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of these two tests was evaluated using Kaplan-Meier methods. Possible human papillomavirus (HPV) types to be cross-reacted by HC2 were also analyzed. The overall agreement between HC2 and SPF₁₀-LiPA for detecting carcinogenic HPV was 73.27%. The highest 10-year cumulative risk of CIN2+ was observed in both HC2 positive and LiPA-carcinogenic HPV positive women (25.70%; 95% confidence interval [CI]=23.55%-27.91%), followed by HC2 positive but LiPA-non-carcinogenic HPV positive women (9.97%; 95% CI=8.57%-11.50%), HC2 negative but LiPA-carcinogenic HPV positive (2.56%; 95% CI=2.44%-2.70%) and HC2 positive but LiPA-HPV negative (1.85%; 95% CI=1.78%-1.92%) women. The proportion of cross-reactivity of HC2 with untargeted carcinogenic types was 8.9%, most of which were attributable to HPV26, 73, 82, 69, 71, 53, 11, 43, and 54. The noticeable high risk of CIN2+ in women infected with cross-reacted non-carcinogenic HPV and low risk in those with miss-to-detective carcinogenic HPV supported an overall good clinical performance of HC2 for a general cervical cancer screening.

  2. [The identification of viruses of human papilloma of high carcinogenic risk and evaluation of physical status of viral DNA using technique of polymerase-chain reaction under affection of cervical epithelium].

    Science.gov (United States)

    Viazovaia, A A; Kuevda, D A; Trofimova, O B; Shipulina, O Iu; Ershov, V A; Lialina, L V; Narvskaia, O V

    2013-08-01

    The DNA of virus of human papilloma of high carcinogenic risk was detected in 116 cervical samples. At that, the morphological symptoms of background processes are detected in 19 samples, CIN 1 in 9, CIN 2 in 23, CIN 3 in 54 (and out of them carcinoma in situ in 13), epidermoid cancer (squamous cell carcinoma) in 11 cases. The viral load of human papilloma of high carcinogenic risk in all samples of DNA exceeded threshold of clinical value (3 lg copies of DNA of human papilloma/105 cells). The genetic typing of human papilloma of high carcinogenic risk revealed the dominance of human papilloma of type 16 in 49.7%, type 33 in 15.3%, type 31 in 12.3% and type 45 in 5.5%. In women with background processes in cervix of the uterus DNA of human papilloma type 16 was detected more often in episome form. In case of dysplastic alterations of epithelium and cervical cancer DNA of human papilloma type 16 is detected in mixt form with different degree of integration into cell genome.

  3. Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells.

    Directory of Open Access Journals (Sweden)

    Ali M Tabish

    Full Text Available In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6 cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2'-deoxycytidine. The effect of exposure on 5-methyl-2'-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic.

  4. Polycyclic Aromatic Hydrocarbons In Edible Mushrooms from Niger Delta, Nigeria: Carcinogenic and Non-Carcinogenic Health Risk Assessment

    Science.gov (United States)

    Igbiri, Sorbari; Udowelle, Nnaemeka Arinze; Ekhator, Osazuwa Clinton; Asomugha, Rose Ngozi; Igweze, Zelinjo Nkeiruka; Orisakwe, Orish Ebere

    2017-02-01

    In the oil-rich Niger Delta, hydrocarbon pollution and oil spillages, gas flaring and sundry anthropogenic activities constitute sources of polycyclic aromatic hydrocarbons (PAHs), with food contamination playing a major role in human exposure. In this study we assessed PAH levels in wild and cultivated edible mushroom species consumed by the general population from the oil producing Niger Delta, Nigeria. The concentrations of USEPA-16 PAHs were determined by gas chromatography and carcinogenic and non-carcinogenic health risks were calculated. The concentrations of USEPA-16 PAHs ranged from 0.02 mg/kg – 3.37 mg/kg. The dietary intake of carcinogenic and non-carcinogenic USEPA-16 PAHs (Naphthalene, Acenaphthylene, Acenaphthene, Anthracene, Phenanthrene, Flourene, Flouranthene, Pyrene, Benzo[a]Anthracene, Chrysene, Benzo[a]Pyrene, Benzo[b]Flouranthene, Benzo[K]Flouranthene, Benzo[g,h,i] Perylene, Dibenz[a,h]Anthracene and Ideno[1,2,3-cd]Pyrene) for adults, adolescents and seniors ranged from 0.00 – 0.05 mg/kg/day, 0.00 – 0.06 mg/kg/day and 0.00 – 0.07 mg/kg/day. The BaPeq ranged from 0.02 – 2.76 with margin of exposure MOE values of BaP ranging from 3,500,000 to 700,000, 3,500,000 and 3,500,000 to 7,000,000 for adults, adolescents and seniors indicating very insignificant health risk. The incremental lifetime cancer risk was within the safe range of 1.56x10-8 – 1.73x10-6 with the highest calculated risk found for wild Pleurotus ostreatus mushroom species from the study area. Creative Commons Attribution License

  5. Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Masayoshi; Usuda, Koji; Hayashi, Seigo; Ogawa, Izumi; Furukawa, Satoshi [Nissan Chemical Industries Limited, Toxicology and Environmental Science Department, Biological Research Laboratories, Saitama (Japan); Igarashi, Maki [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Nakae, Dai [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Tokyo Metropolitan Institute of Public Health, Tokyo (Japan)

    2008-08-15

    Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p. injection of N-nitrosodiethylamine at a dose of 200 mg/kg b.w. as a carcinogenic initiator. Starting 2 weeks thereafter, rats received 0, 10, 300 or 6,000 ppm of copper gluconate in diet for 6 weeks. All rats underwent 2/3 partial hepatectomy at the end of week 3, and all surviving rats were killed at the end of week 8. In the short-term experiment, rats were given 0, 10, 300 or 6,000 ppm of copper gluconate for 2 weeks. Numbers of glutathione S-transferase placental form (GST-P) positive lesions, single GST-P-positive hepatocytes and 8-oxoguanine-positive hepatocytes, and levels of cell proliferation and apoptosis in the liver were significantly increased by 6,000 ppm of copper gluconate in the medium-term liver bioassay. Furthermore, hepatic mRNA expression of genes relating to the metal metabolism, inflammation and apoptosis were elevated by 6,000 ppm of copper gluconate both in the medium-term liver bioassay and the short-term experiments. These results indicate that copper gluconate possesses carcinogenic risk toward the liver at the high dose level, and that oxidative stress and inflammatory and pro-apoptotic signaling statuses may participate in its underlying mechanisms. (orig.)

  6. Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Boersma, M.G.; Woude, van der H.; Jeurissen, S.M.F.; Schutte, M.E.; Alink, G.M.

    2005-01-01

    The present review focuses on the mechanisms of mutagenic action and the carcinogenic risk of two categories of botanical ingredients, namely the flavonoids with quercetin as an important bioactive representative, and the alkenylbenzenes, namely safrole, methyleugenol and estragole. For quercetin a

  7. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Levels of Genotoxic and Carcinogenic Compounds in Plant food Supplements and Associated Risk Assessment

    NARCIS (Netherlands)

    Berg, van den S.J.P.L.; Restani, P.; Boersma, M.G.; Delmulle, L.; Rietjens, I.

    2011-01-01

    The present study describes the selection, analysis and risk assessment of genotoxic and carcinogenic compounds of botanicals and botanical preparations which can be found in plant food supplements (PFS). First an inventory was made of botanical compounds that are of possible concern for human healt

  9. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-09-01

    There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was

  10. Binding of chemical carcinogens to macromolecules in cultured human colon

    DEFF Research Database (Denmark)

    1977-01-01

    Metabolic activation of different chemical classes of carcinogens was studied in cultured human colon epithelia. Human colon epithelia were maintained in explant culture up to 4 days. Binding of benzo(a)pyrene, dimethylnitrosamine, and 1,2- dimethylhydrazine was found in both cell DNA and protein....... 1,2-Dimethylhydrazine methylated DNA at both N·7 and 0-6 positions of guanin....

  11. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical......A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...... for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

  12. A theoretical concept of low level/low LET radiation carcinogenic risk (LLCR) projection

    Energy Technology Data Exchange (ETDEWEB)

    Filyushkin, I.V. [Laboratory of Theoretical Radiobiology, Moscow (Russian Federation)

    1992-06-01

    Carcinogenic risk to humans resulting from low level/low LET radiation exposure (LLLCR) has not been observed directly because epidemiological observations have not yet provided statistically significant data on risk values. However, these values are of great interest for radiation health science and radiation protection practice under both normal conditions and emergency situations. This report presents a theoretical contribution to the validation of dose and dose rate efficiency factors (DDREF) transforming cocinogenic risk coefficients from those revealed in A-bomb survivors to factors appropriate for the projection of the risk resulting from very low levels of low LET radiation.

  13. Prevalence of genotoxic chemicals among animal and human carcinogens evaluated in the IARC Monograph Series.

    Science.gov (United States)

    Bartsch, H; Malaveille, C

    1989-06-01

    To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in humans and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and on agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and 3. The results of this analysis indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage and chromosomal/mutational damage) may represent a hazard to humans; and b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall, this analysis implies that genotoxic carcinogens add more to the cancer burden in man than non-genotoxic carcinogens. Thus, identification of such genotoxic carcinogens and subsequent lowering of exposure will remain the main goal for primary cancer prevention in man.

  14. The carcinogenic risks of low-LET and high-LET ionizing radiations. Revision

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I. [Lawrence Berkeley Lab., CA (United States)]|[California Univ., San Francisco, CA (United States)

    1991-08-01

    This report presents a discussion on risk from ionizing radiations to human populations. Important new information on human beings has come mainly from further follow-up of existing epidemiological studies, notably the Japanese atomic bomb survivors and the ankylosing spondylitis patients; from new epidemiological surveys, such as the patients treated for cancer of the uterine cervix; and from combined surveys, including workers exposed in underground mines. Since the numerous and complex differences among the different study populations introduce factors that influence the risk estimates derived in ways that are not completely understood, it is not clear how to combine the different risk estimates obtained. These factors involve complex biological and physical variables distributed over time. Because such carcinogenic effects occur too infrequently to be demonstrated at low doses, the risks of low-dose radiation can be estimated only by interpolation from observations at high doses on the basis of theoretical concepts, mathematical models and available empirical evidence, primarily the epidemiological surveys of large populations exposed to ionizing radiation. In spite of a considerable amount of research, only recently has there has been efforts to apply the extensive laboratory data in animals to define the dose-incidence relationship in the low dose region. There simply are insufficient data in the epidemiological studies of large human populations to estimate risk coefficients directly from exposure to low doses. The risk estimates for the carcinogenic effects of radiation have been, in the past, somewhat low and reassessment of the numerical values is now necessary.

  15. The carcinogenic risks of low-LET and high-LET ionizing radiations

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I. (Lawrence Berkeley Lab., CA (United States) California Univ., San Francisco, CA (United States))

    1991-08-01

    This report presents a discussion on risk from ionizing radiations to human populations. Important new information on human beings has come mainly from further follow-up of existing epidemiological studies, notably the Japanese atomic bomb survivors and the ankylosing spondylitis patients; from new epidemiological surveys, such as the patients treated for cancer of the uterine cervix; and from combined surveys, including workers exposed in underground mines. Since the numerous and complex differences among the different study populations introduce factors that influence the risk estimates derived in ways that are not completely understood, it is not clear how to combine the different risk estimates obtained. These factors involve complex biological and physical variables distributed over time. Because such carcinogenic effects occur too infrequently to be demonstrated at low doses, the risks of low-dose radiation can be estimated only by interpolation from observations at high doses on the basis of theoretical concepts, mathematical models and available empirical evidence, primarily the epidemiological surveys of large populations exposed to ionizing radiation. In spite of a considerable amount of research, only recently has there has been efforts to apply the extensive laboratory data in animals to define the dose-incidence relationship in the low dose region. There simply are insufficient data in the epidemiological studies of large human populations to estimate risk coefficients directly from exposure to low doses. The risk estimates for the carcinogenic effects of radiation have been, in the past, somewhat low and reassessment of the numerical values is now necessary.

  16. Potential health risks related to carcinogens in the atmospheric environment in India.

    Science.gov (United States)

    Gurjar, B R; Mohan, M; Sidhu, K S

    1996-10-01

    In India, rapid urbanization and industrialization have contributed positively toward meeting the materialistic needs of the citizens, but have also resulted in contamination of the atmospheric environment. This paper deals with the assessment of potential health risks posed by carcinogenic substances, namely cadmium, chromium, and nickel, present in certain atmospheric environments in India. Average air concentrations of these carcinogenic metals have been assessed for different states and regions of India (C. R. Krishnamurti and P. Vishwanathan, Toxic Metals in the Indian Environment, Tata/McGraw-Hill, New Delhi, 1991). Based on these assessments, both individual and societal risks have been estimated in different states of the country, and comparisons were made. Reported concentration, release sources, potential health risks including cancer risk estimates, and ambient air interim guidelines are discussed. The reported environmental releases and cancer risk from cadmium are minimal. There is a potential for increased respiratory cancer risk from exposure to chromium and nickel in some northern Indian states. These metals are irritants to nasal passages and the respiratory tract. Chromium is also corrosive to mucus membranes. They have the potential to cause chronic respiratory problems. Since it appears that these metals may cause some adverse health effects in humans, exposure to these ambient air pollutants should be minimized by managing the release of these contaminants to the environment. There is a need for the development and strict enforcement of national and state regulatory standards.

  17. The use of mechanistic data and the handling of scientific uncertainty in carcinogen risk assessments. The trichloroethylene example.

    Science.gov (United States)

    Rudén, Christina

    2002-02-01

    The purpose of this paper is to explore how risk assessors actually use mechanistic data in carcinogen risk assessment and to discuss how the handling of scientific uncertainty may affect the outcome of the risk assessment. The analysis is performed by comparing 29 trichloroethylene risk assessment documents in general and 2 of these, namely the ECETOC (1994, Trichloroethylene: Assessment of Human Carcinogenic Hazard, Technical Report No. 60) and the OECD/EU (1996, Initial Assessment Report for the 4th SIAM (Screening Information Data Set Initial Assessment Meeting), May 1996: Trichloroethylene, sponsor country, United Kingdom [Draft]), in more detail. It is concluded that in this example the ECETOC required less evidence for considering a carcinogenic mechanism irrelevant to humans than did the OECD/EU risk assessors. There are examples of when two risk assessors have selected different primary data for their argumentation and also examples of how one and the same primary publication was interpreted differently. Biased data selection and evaluation of primary data that correlate to the risk assessor's overall conclusions have also been identified. The general comparison of all 29 TCE risk assessment documents indicates that the assessment of scientific uncertainty in the mechanistic data affects the overall conclusions.

  18. Breast cancer in intraductal carcinogen-treated non-human primates.

    Science.gov (United States)

    Lillie, Madeline A; Ambrus, Clara M; Pickren, John W; Akhter, Selina; Islam, Abul; Ambrus, Julian L

    2004-01-01

    Eight female Macaca arctoides monkeys were given dimethylbenzanthracene (DMBA) directly into the milk ducts. During a 4-year observation period, ending with euthanasia and autopsy, no mammary cancers were noticed. However, one animal developed a superficial localized squamous cell carcinoma. DMBA is highly carcinogenic in rodents, e.g. producing a high incidence of breast cancer in C3H mice. It was concluded that carcinogenicity testing should be extended beyond testing in rodents to non-human primates in order to distinguish "primary rodent carcinogens" from those highly active in primates as well. Studies are in progress to study carcinogens in human cell lines transplanted into nu/nu mice.

  19. Regulatory Forum Opinion Piece: Carcinogen Risk Assessment: The Move from Screens to Science.

    Science.gov (United States)

    Downes, Noel; Foster, John

    2015-12-01

    Throughout the last 50 years, the paradigm for carcinogenicity assessment has depended on lifetime bioassays in rodents. Since 1997, the International Conference on Harmonisation (ICH) S1B has permitted the use of a 2-year rodent bioassay (usually in the rat) and an alternative, genetically modified mouse model to support cancer risk assessment of pharmaceuticals. Since its introduction, it has become apparent that many of the stated advantages of the 6-month Tg mouse bioassay have, in actual fact, not been realized, and the concern exists that an albeit imperfect, 2-year mouse bioassay has been replaced by a similarly imperfect 6-month equivalent. This essay argues strongly that model systems, using cancer as the end point, should be discontinued, and that the recent initiatives, from the Organization for Economic Cooperation and Development and Institute of Peace and Conflict Studies, on "mode of action," "adverse outcome pathways," and "human relevance framework" should be embraced as being risk assessments based upon the available science. The recent suggested revisions to the ICH S1 guidelines, utilizing carcinogenicity assessment documents, go some way to developing a science-based risk assessment that does not depend almost entirely on a single, imperfect, cancer-based end point in nonrelevant animal species.

  20. Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation.

    Science.gov (United States)

    Berger, M R

    1991-01-01

    This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long-term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy.

  1. The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene—Two Emerging Potential Human Carcinogens?

    Directory of Open Access Journals (Sweden)

    Alex O. Okaru

    2017-03-01

    Full Text Available For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The World Health Organization (WHO International Agency for Research on Cancer (IARC continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene are potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages, while β-myrcene occurs naturally as a constituent of the essential oils of plants such as hops, lemongrass, and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using literature review data. Additionally, results of furfuryl alcohol occurrence from our own nuclear magnetic resonance (NMR analysis are included. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg and in some fish products (about 10 mg/kg, while among beverages, wines contained between 1 and 10 mg/L, with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

  2. [Cardiovascular risk, occupation and exposure to occupational carcinogens in a group of workers in Salamanca].

    Science.gov (United States)

    González-Sánchez, Jesús

    2015-01-01

    Identify the cardiovascular risk factors in a group of workers in the province of Salamanca, protected by external prevention services, as regards exposure to occupational carcinogens, by sector of activity and gender. An observational descriptive epidemiological study was conducted. The sample selection was by stratified random sampling in each entity. The variables collected by questionnaire were, sociodemographic characteristics, exposure to occupational carcinogens, and cardiovascular risk factors (smoking, hypertension, dyslipidemia, and diabetes), using the clinical-work histories as a source of information. Statistically significant differences were observed in cardiovascular risk according to the exposure to occupational carcinogens (p cardiovascular risk in the work place. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  3. [Using the evaluation of carcinogenic risk in the mining and metallurgical enterprises of the Arctic].

    Science.gov (United States)

    Serebriakov, P V

    2012-01-01

    The aim of this study--hygienic assessment of the contribution of factors of working environment) in the formation of carcinogenic risk to the mining and metallurgical enterprises of the Far North, the establishment of the structural features of cancer pathology among workers of these enterprises, quantitative evaluation of individual professional cancer risk in different nosological forms and morphological variants of malignant neoplasms.

  4. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

  5. Carcinogenic risks associated with radiation pollution. [UV radiation, sunlight

    Energy Technology Data Exchange (ETDEWEB)

    Latarjet, R.

    1976-01-01

    The cancerogenic pollution by non-ionizing radiations is limited to the case of solar ultraviolet, whose activity at ground level may be increased as a consequence of the stratospheric depletion of ozone, produced by certain chemical pollutants: nitrogen oxides from supersonic aircrafts, freon. As regards ionizing radiations, the discussion is focused on the fundamental problem of the threshold, and on the means by which one may obtain some quantitative data related to carcinogenesis by small radiation doses in man. A new concept, that of a practical threshold, is proposed. A theory which links radiocancerogenesis, as well as chemical cancerogenesis, to errors produced in the repair of lesions in the DNA is discussed. The rads-equivalent project for chemical mutagens and carcinogens is described.

  6. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

    Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

  7. Assessing carcinogenic risks associated with ingesting arsenic in farmed smeltfish (Ayu, Plecoglossus altirelis) in aseniasis-endemic area of Taiwan.

    Science.gov (United States)

    Lee, Jin-Jing; Jang, Cheng-Shin; Liang, Ching-Ping; Liu, Chen-Wuing

    2008-09-15

    This study spatially analyzed potential carcinogenic risks associated with ingesting arsenic (As) contents in aquacultural smeltfish (Plecoglossus altirelis) from the Lanyang Plain of northeastern Taiwan. Sequential indicator simulation (SIS) was adopted to reproduce As exposure distributions in groundwater based on their three-dimensional variability. A target cancer risk (TR) associated with ingesting As in aquacultural smeltfish was employed to evaluate the potential risk to human health. The probabilistic risk assessment determined by Monte Carlo simulation and SIS is used to propagate properly the uncertainty of parameters. Safe and hazardous aquacultural regions were mapped to elucidate the safety of groundwater use. The TRs determined from the risks at the 95th percentiles exceed one millionth, indicating that ingesting smeltfish that are farmed in the highly As-affected regions represents a potential cancer threat to human health. The 95th percentile of TRs is considered in formulating a strategy for the aquacultural use of groundwater in the preliminary stage.

  8. Biological effect markers for exposure to carcinogenic compound and their relevance for risk assessment

    NARCIS (Netherlands)

    Delft, J.H.M. van; Baan, R.A.; Roza, L.

    1998-01-01

    In this review data are summarized on biomarkers that are used for biological effect monitoring of human populations exposed to genotoxic carcinogens. The biomarkers are DNA and protein adducts and cytogenetic effects. Most of these biomarkers are relevant for the process of carcinogenesis. Emphasis

  9. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Predicting the carcinogenicity of chemicals in humans from rodent bioassay data

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, G. (Harvard Univ., Cambridge, MA (United States) School of Public Health, Boston, MA (United States)); Wilson, R. (Harvard Univ., Cambridge, MA (United States))

    1991-08-01

    Regulatory agencies currently rely on rodent carcinogenicity bioassay data to predict whether or not a given chemical poses a carcinogenic threat to humans. The authors argue that it is always more useful to know a chemical's carcinogenic potency (with confidence limits) than to be able to say only qualitatively that it has been found to be a carcinogen. In a typical bioassay, a chemical is administered to groups of 50 to 100 rodents at the highest feasible level (the maximum tolerated dose) and rarely at less than 1/10 this dose in order to maximize the statistical significance of any increase in tumors that might result. Recently, much experimental work has focused on the mechanisms by which site-specific toxicity arising from chronic administration at the maximum tolerated dose may lead to carcinogenicity. Extrapolation of high-dose results to low dose does not take into consideration the possibility of a threshold dose, below which the carcinogenic potency is much lower or even zero. Threshold dose-response phenomena may be much more relevant to the etiology of cancer in the rodent bioassays than was earlier realized; if so, there is an even greater need for establishing dose-dependent potency estimates. The emphasis of this review is in the interspecies comparison of high-dose potencies. The qualitative and quantitative comparison of carcinogenicities between mice and rats and between rodents and humans is reviewed and discussed. They conclude that there is a good qualitative (yes/no) correlation for both the rat/mouse and the rodent/human comparison.

  11. Carcinogen testing. Fact and fallacy.

    Science.gov (United States)

    Moore, J A

    1988-10-15

    In the absence of human information on the carcinogenicity of chemical substances, one must rely primarily on information from long-term animal testing. Although far from perfect, animal studies seem to be reasonable predictors of the human experience, both qualitatively and quantitatively. Short-term tests for genotoxicity may be helpful for establishing priorities for chemical testing, but they are not as strong indicators of potential carcinogenicity as had been previously thought. New directions in toxicologic research hold the promise for scientists being able to perform more reasoned assessments of carcinogenic risk.

  12. Heavy incense burning in temples promotes exposure risk from airborne PMs and carcinogenic PAHs.

    Science.gov (United States)

    Chiang, Kuo-Chih; Liao, Chung-Min

    2006-12-15

    We present the mechanistic-based exposure and risk models, appraised with reported empirical data, to assess how the human exposure to airborne particulate matters (PMs) and carcinogenic polycyclic aromatic hydrocarbons (PAHs) during heavy incense burning episodes in temples. The models integrate size-dependent PM levels inside a temple from a published exploratory study associated with a human expiratory tract (HRT) model taking into account the personal exposure levels and size distributions in the HRT. The probabilistic exposure profiles of total-PAH levels inside a temple and internal PAHs doses are characterized by a physiologically based pharmacokinetic (PBPK) model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing PAHs toxicity for DNA adducts formation and lung tumor incidence responses in human white blood cells and lung. Results show that the alveolar-interstitial (AI) region has a lower mass median diameter (0.29 microm) than that in extrathoracic (ET(1), 0.37 microm), brochial (BB, 0.36 microm) and bronchiolar (bb, 0.32 microm) regions. The 50% probability (risk=0.5) of exceeding the DNA adducts frequency (DA(f)) ratio of 1.28 (95% CI: 0.55-2.40) and 1.78 (95% CI: 0.84-2.95) for external exposure of B[a]P and B[a]P(eq), respectively. The 10% (risk=0.1) probability or more of human affected by lung tumor is approximately 7.62x10(-5)% (95% CI: 3.39x10(-5)-1.71x10(-4)%) and 3.87x10(-4)% (95% CI: 1.72x10(-4)-8.69x10(-4)%) for internal exposure of B[a]P and B[a]P(eq), respectively. Our results implicate that exposure to smoke emitted from heavy incense burning may promote lung cancer risk. Our study provides a quantitative basis for objective risk prediction of heavy incense burning exposure in temples and for evaluating the effectiveness of management.

  13. Human exposure to carcinogenic heterocyclic amines and their mutational fingerprints in experimental animals.

    Science.gov (United States)

    Nagao, M; Wakabayashi, K; Ushijima, T; Toyota, M; Totsuka, Y; Sugimura, T

    1996-01-01

    Heterocyclic amines (HCAs) are mutagens/carcinogens to which humans are exposed on almost a daily basis. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) is the most abundant of the various carcinogenic HCAs (present at a level of 0.56 to 69.2 ng/g of cooked meat or fish), with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) following it at 0.64 to 6.44 ng/g. HCAs have been found in the urine of healthy people who consume ordinary diets, while patients receiving parenteral alimentation lack, for example, PhlP and MelQx in their urine. Based on the concentrations of PhlP and MelQx in urine samples from 10 healthy volunteers, daily intake of MelQx in Japanese was calculated to be 0.3 to 3.9 micrograms/person, while that of PhlP was 0.005 to 0 micrograms. The Japanese consume more MelQx than Americans, whereas Japanese intake of PhlP was about one-third that of Americans. MelQx-DNA adducts have also detected in Japanese Kidney, colon, and rectum samples using the 32P-postlabeling method followed by identification using high-performance liquid chromatography (HPLC) analysis; the levels were 0.18, 1.8, and 1.4 per 10(9) nucleotides, respectively. In addition, we elucidated the mutational fingerprints of Phlp by analyzing Apc mutations in rat colon cancers induced by this carcinogen. Four of eight tumors had a total of five mutations in the Apc gene, four of which featured a guanine deletion from 5'-GTGGGAT-3' sequences. This specific mutation spectrum may be used as a fingerprint of PhlP in evaluating its risk potential for human colon carcinogenesis. Mutations were not found in similar 2-amino-3-methylimidazo[4,5-f]quinoline-induced colon lesions. Microsatellite instability was detected in both colon and mammary tumors induced by PhlP. The mechanisms involved in this development of microsatellite instability in PhlP. The mechanisms involved in this development of microsatellite instability in PhlP-induced cancers remain to be elucidated. Images Figure 1

  14. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    DEFF Research Database (Denmark)

    Kuempel, Eileen D.; Jaurand, Marie-Claude; Møller, Peter

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based...... on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting...... in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials...

  15. 17. Exposure and Metabolism of Heterocyclic Amine Food Mutagens/Carcinogens in Humans

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Carcinogens produced from overcooked foods are extremely mutagenic in numerous in vitro and in vivo test systems. One of these mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) induces breast, colon and prostate tumors in rats and has been implicated in dietary epidemiology studies for raising the risk of

  16. Carcinogenic risk assessment for emissions from clinical waste incineration and road traffic.

    Science.gov (United States)

    Wheatley, Andrew; Sadhra, Steven

    2010-10-01

    The most significant potentially carcinogenic substances arising from a state-of-the-art clinical waste incinerator (CWI) and vehicle emissions were identified as polychlorinated dibenzo-p-dioxins, polycyclic aromatic hydrocarbons (PAHs), benzene, 1-butadiene, arsenic, cadmium, chromium and nickel. Long-term exposures of the notional maximum exposed individual (MEI) in the local environment, together with aggregate emissions from transport of clinical waste, were estimated. Mass emission rates of PAHs from the CWI to air were compared with previously published estimates of mass emissions to land from CWI bottom ash. Aggregate emissions from road transport of clinical waste were of a similar order to stack emissions from incineration. Mass emissions of PAHs to landfill generally greatly exceeded those from stack emissions. Emissions associated with operation of the CWI present a negligible contribution to overall cancer risk from PAHs and other carcinogens. Uncertainty in the quantitative risk estimates presented here is discussed in the context of these findings.

  17. Human cytochrome P450 enzyme specificity for bioactivation of safrole to the proximate carcinogen 1'-hydroxysafrole

    NARCIS (Netherlands)

    Jeurissen, S.M.F.; Bogaards, J.J.P.; Awad, H.M.; Boersma, M.G.; Brand, W.; Fiamegos, Y.C.; Beek, van T.A.; Alink, G.M.; Sudhölter, E.J.R.; Cnubben, N.H.P.; Rietjens, I.M.C.M.

    2004-01-01

    In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1'-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1'-hydroxylation of safrole was characterized in a variety of in vitro te

  18. An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether (Egbe)

    Science.gov (United States)

    This position paper, An Evaluation of the Human Carcinogenic Potential of Ethylene Glycol Butyl Ether, was developed in support of the EPA's evaluation of a petition from the American Chemistry Council requesting to delist EGBE per the Clean Air Act Amendments (CAAA), Titl...

  19. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    Directory of Open Access Journals (Sweden)

    Gasser Robin B

    2007-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CCA – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum than to free-living (Schmidtea mediterranea flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions

  20. Chemical characteristic of PM2.5 emission and inhalational carcinogenic risk of domestic Chinese cooking.

    Science.gov (United States)

    Zhang, Nan; Han, Bin; He, Fei; Xu, Jia; Zhao, Ruojie; Zhang, Yujuan; Bai, Zhipeng

    2017-08-01

    To illustrate chemical characteristic of PM2.5 emission and assess inhalational carcinogenic risk of domestic Chinese cooking, 5 sets of duplicate cooking samples were collected, using the most used 5 types of oil. The mass abundance of 14 elements, 5 water-soluble ions, organic carbon (OC), elemental carbon (EC) and 11 polycyclic aromatic hydrocarbons (PAHs) were calculated; the signature and diagnostic ratio of cooking in the domestic kitchen were analyzed; and carcinogenic risks of heavy metals and PAHs via inhalation were assessed in two scenarios. The analysis showed that OC was the primary composition in the chemical profile; Na was the most abundant element that might be due to the usage of salt; Cr and Pb, NO3(-) and SO4(2-), Phe, FL and Pyr were the main heavy metals/water-soluble ions/PAHs, respectively. Phe and FL could be used to separate cooking and stationary sources, while diagnostic ratios of BaA/(BaA + CHR), BaA/CHR, BaP/BghiP and BaP/BeP should be applied with caution, as they were influenced by various cooking conditions. Carcinogenic risks of heavy metals and PAHs were evaluated in two scenarios, simulating the condition of cooking with no ventilation and with the range hood on, respectively. The integrated risk of heavy metals and PAHs was 2.7 × 10(-3) and 5.8 × 10(-6), respectively, during cooking with no ventilation. While with the usage of range hood, only Cr(VI), As and Ni might induce potential carcinogenic risk. The difference in the chemical abundance in cooking sources found between this and other studies underlined the necessity of constructing locally representative source profiles under real conditions. The comparison of carcinogenic risk suggested that the potentially adverse health effects induced by inorganic compositions from cooking sources should not be ignored. Meanwhile, intervention methods, such as the operation of range hood, should be applied during cooking for health protection. Copyright © 2017 Elsevier Ltd

  1. Environmental exposure to human carcinogens in teenagers and the association with DNA damage

    DEFF Research Database (Denmark)

    Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie

    2017-01-01

    Background We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two...... areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds...... was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP...

  2. Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: An immunohistochemistry study

    Energy Technology Data Exchange (ETDEWEB)

    Pratt, M. Margaret [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States)], E-mail: prattm@mail.nih.gov; Sirajuddin, Paul; Poirier, Miriam C. [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States); Schiffman, Mark [Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD (United States); Glass, Andrew G.; Scott, David R.; Rush, Brenda B. [Northwest Kaiser Permanente, Portland, OR (United States); Olivero, Ofelia A. [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States); Castle, Philip E. [Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD (United States)

    2007-11-01

    Among women infected with carcinogenic human papillomavirus (HPV), there is a two- to five-fold increased risk of cervical precancer and cancer in women who smoke compared to those who do not smoke. Because tobacco smoke contains carcinogenic polycyclic aromatic hydrocarbons (PAHs), it was of interest to examine human cervical tissue for PAH-DNA adduct formation. Here, we measured PAH-DNA adduct formation in cervical biopsies collected in follow-up among women who tested positive for carcinogenic HPV at baseline. A semi-quantitative immunohistochemistry (IHC) method using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was used to measure nuclear PAH-DNA adduct formation. Cultured human cervical keratinocytes exposed to 0, 0.153, or 0.331 {mu}M BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N{sup 2}deoxyguanosyl)-7,8,9, 10-tetrahydro-benzo[a]pyrene (BPdG) adducts. For BPdG adduct analysis, paraffin-embedded keratinocytes were stained by IHC with analysis of nuclear color intensity by Automated Cellular Imaging System (ACIS) and, in parallel cultures, extracted DNA was assayed by quantitative BPDE-DNA chemiluminescence immunoassay (CIA). For paraffin-embedded samples from carcinogenic HPV-infected women, normal-appearing cervical squamous epithelium suitable for scoring was found in samples from 75 of the 114 individuals, including 29 cases of cervical precancer or cancer and 46 controls. With a lower limit of detection of 20 adducts/10{sup 8} nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/10{sup 8} nucleotides, with a median of 75/10{sup 8} nucleotides. PAH-DNA adduct values above 150/10{sup 8} nucleotides were found in eight samples, and in three samples adducts were non-detectable. There was no correlation between PAH-DNA adduct formation and either smoking or case status. Therefore, PAH-DNA adduct formation as measured by this methodology did not appear

  3. Spatial analysis of potential carcinogenic risks associated with ingesting arsenic in aquacultural tilapia (Oreochromis mossambicus) in blackfoot disease hyperendemic areas.

    Science.gov (United States)

    Jang, Cheng-Shin; Liu, Chen-Wuing; Lin, Kao-Hung; Huang, Feng-Mei; Wang, Sheng-Wei

    2006-03-01

    This work analyzed spatially potential carcinogenic risks associated with ingesting arsenic (As) contents in aquacultural tilapia (Oreochromis mossambicus) in coastal regions of southwestern Taiwan, where the blackfoot disease prevails. Sequential indicator simulation (SIS) was used to reproduce As exposure distributions in groundwater based on their three-dimensional variability. A target cancer risk (TR) associated with ingesting As in aquacultural tilapia was calculated to evaluate the potential risk to human health. Owing to sparse measured data, Monte Carlo simulation and SIS properly accounted for the uncertainty of assessed parameters. The probabilistic risk assessment formulated suitable strategies under various remedial stages. Aquacultural regions with high risks were mapped to elucidate the safety of groundwater use at different depths. Many TRs determined from the risks at the 75th and 95th percentiles exceed one millionth in the regions, indicating that ingesting tilapia farmed in the highly As-polluted regions poses potential cancer threats to human health. The 75th percentile of TR is considered in formulating a remedial strategy for the aquacultural use of groundwater in the preliminary stage. Additionally, this study suggests reducing the use of groundwater in aquaculture or changing the depths from which groundwater is withdrawn in the areas with high risks of cancer.

  4. The carcinogenic risks of low-LET and high-LET ionizing radiations

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I. (Lawrence Berkeley Lab., CA (USA))

    1989-08-01

    New information is available concerning the carcinogenic effects of radiation and the implications for risk assessment and risk management. This information comes from further follow-up of the epidemiological studies of the Japanese atomic bomb survivors, patients irradiated medically for cancer and allied conditions, and workers exposed in various occupations. In the Japanese atomic bomb survivors the carcinogenic risks are estimated to be somewhat higher than previously, due to the reassessment of the atomic-bomb dosimetry, further follow-up with increase in the number of excess cancer deaths, particularly in survivors irradiated early in life, and changes in the methods of analysis to compute the age-specific risks of cancer. Because of the characteristics of the atomic bomb survivor series as regards sample size, age and sex distribution, duration for follow-up, person-years at risk, and type of dosimetry, the mortality experience of the atomic bomb survivors was selected by the UNSCEAR Committee and the BEIR V Committee as the more appropriate basis for projecting risk estimates for the general population. In the atomic bomb survivors, the dose-effect relationship for overall cancer mortality other than leukemia is consistent with linearity below 3 Gy, while the dose-effect relationship for leukemia, excluding chronic lymphatic leukemia, conforms best to a linear-quadratic function. The shape of the dose-incidence curve at low doses still remains uncertain, and the data do not rule out the possible existence of a threshold for an neoplasm. The excess relative risk of mortality from all cancers combined is estimated to be 1.39 per Gy (shielded kerma), which corresponds to an absolute risk of 10.0 excess cancer deaths per 10,000 PYGy; the relative risks is 1.41 at 1 Gy (organ-absorbed dose), and an absolute risk of 13.07 excess cancer deaths per 10,000 PYGy. 19 refs.

  5. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection.

    Science.gov (United States)

    Vriend, Henrike J; Bogaards, Johannes A; van Bergen, Jan E A M; Brink, Antoinette A T P; van den Broek, Ingrid V F; Hoebe, Christian J P A; King, Audrey J; van der Sande, Marianne A B; Wolffs, Petra F G; de Melker, Hester E

    2015-10-01

    We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation trial, swabs were polymerase chain reaction tested to detect chlamydia and 14 carcinogenic HPV genotypes. HPV type-specific incidence and persistence rates were stratified for chlamydia positivity at follow-up. Associations were assessed by multilevel logistic regression analyses with correction for sexual risk factors. HPV type-specific incidence ranged from 1.4% to 8.9% and persistence from 22.7% to 59.4% after a median follow-up of 11 months (interquartile range: 11-12). Differences in 1-year HPV persistence rates between chlamydia -infected and noninfected women were less distinct than differences in HPV incidence rates (pooled adjusted odds ratios of 1.17 [95% CI: 0.69-1.96] and 1.84 [95% CI: 1.36-2.47], respectively). The effect of chlamydia co-infection on HPV-infection risk did not significantly differ by HPV genotype. In conclusion, infection with chlamydia increases the risk of infection by carcinogenic HPV types and may enhance persistence of some HPV types. Although these findings could reflect residual confounding through unobserved risk factors, our results do give reason to explore more fully the association between chlamydia and HPV type-specific acquisition and persistence. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  6. Opisthorchis viverrini:The carcinogenic human liver fluke

    Institute of Scientific and Technical Information of China (English)

    Natthawut Kaewpitoon; Soraya J Kaewpitoon; Prasit Pengsaa; Banchob Sripa

    2008-01-01

    Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia,including Thailand,Lao PDR,Vietnam and Cambodia.The infection is associated with a number of hepatobiliary diseases,including cholangitis,obstructive jaundice,hepatomegaly,cholecystitis and cholelithiasis.Multi-factorial etiology of cholangiocarcinoma,mechanical damage,parasite secretions,and immunopathology may enhance cholangiocarcinogenesis.Moreover,both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma,cancer of the bile ducts.The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region,particularly in rural areas,of Thailand.The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.

  7. Effect of chemical mutagens and carcinogens on gene expression profiles in human TK6 cells.

    Directory of Open Access Journals (Sweden)

    Lode Godderis

    Full Text Available Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes, we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose-response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti- apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control.

  8. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far we...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

  9. Human exposure to carcinogens in ambient air in Denmark, Finland and Sweden

    Science.gov (United States)

    Fauser, P.; Ketzel, M.; Becker, T.; Plejdrup, M. S.; Brandt, J.; Gidhagen, L.; Omstedt, G.; Skårman, T.; Bartonova, A.; Schwarze, P.; Karvosenoja, N.; Paunu, V.-V.; Kukkonen, J.; Karppinen, A.

    2017-10-01

    The concentrations of seventeen pollutants (particulate mass fractions PM2.5 and PM10, a range of metals, inorganic gases and organic compounds) are for the first time analyzed in a screening of the carcinogenic risk at a resolution of 1 × 1 km2 in ambient air in three Nordic countries. Modelled annual mean air concentrations in 2010 show no exceedances of the EU air quality limit, guideline or target values. The only modelled exceedance of US-EPA 1:100,000 cancer risk concentrations (0.12 ng/m3, US-EPA IRIS, 2015) occurs for B(a)P in Denmark, for approximately 80% of the Danish population. However, the EU target value threshold of 1 ng/m3 for B(a)P is not exceeded in the modelled values in any parts of Denmark. No emission data for B(a)P were available for the whole domain of the other two considered Nordic countries and important uncertainties are still related to the emissions. Long-range transport is significant for the concentrations of all of the considered pollutants, except for B(a)P that commonly originates mostly from local residential wood combustion. The ambient air concentrations of NOx, SO2, Cd, Cr and Pb also have significant contributions from national sources; 45-65% for NOx and SO2, and for the metals from 15 to 60% in urban areas and from 1 to 20% in rural areas, within the considered Nordic area. High national contributions occur especially in urban air, due to primarily road traffic, residential wood combustion, energy production and industrial point sources. It is recommended to monitor the influence from residential wood combustion more extensively, and to analyze longer time trends for long-term human exposure.

  10. Reshaping the carcinogenic risk assessment of medicines: international harmonisation for drug safety, industry/regulator efficiency or both?

    Science.gov (United States)

    Abraham, John; Reed, Tim

    2003-07-01

    The most significant institutional entity involved in the harmonisation of drug testing standards worldwide is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), which comprises the three pharmaceutical industry associations and regulatory agencies of the EU, US and Japan. It is often claimed that such harmonisation will both accelerate the development and approval of new drugs and preserve safety standards, if not strengthen safety regimes. Drawing on extensive documentary research and interviews, this paper systematically examines whether the efforts by the ICH to improve industrial and regulatory efficiency by harmonising drug testing requirements is likely to raise, maintain or compromise safety standards in carcinogenic risk assessment of pharmaceuticals. The evidence suggests that, in the field of carcinogenicity testing, the ICH management of international harmonisation of medicines regulation is not achieving simultaneous improvements in safety standards and acceleration of drug development. Rather, the latter is being achieved at the expense of the former. Indeed, the ICH may be converting permissive regulatory practices of the past into new scientific standards for the future. These findings are significant as many expert scientific advisers to drug regulatory agencies seem to have accepted uncritically the conclusions reached by the ICH, which may affect a potential patient population of half a billion and tens of thousands of clinical trials.

  11. The function and significance of SELENBP1 downregulation in human bronchial epithelial carcinogenic process.

    Directory of Open Access Journals (Sweden)

    Gu-Qing Zeng

    Full Text Available BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein 1 (SELENBP1 was progressively decreased in human bronchial epithelial carcinogenic process. However, there is little information on expression and function of SELENBP1 during human lung squamous cell cancer (LSCC carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in the human bronchial epithelial carcinogenic process. SELENBP1, member of selenoproteins family and progressively downregulated in this process, was selected to further study. Both Western blotting and immunohistochemistry were performed to detect SELENBP1 expression in independent sets of tissues of bronchial epithelial carcinogenesis, and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium from preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1 downregulation on the susceptibility of benzo(apyrene (B[a]P-induced human bronchial epithelial cell transformation were determined. RESULTS: 102 differentially expressed proteins were identified by quantitative proteomics, and SELENBP1 was found and confirmed being progressively decreased in the human bronchial epithelial carcinogenic process. The sensitivity and specificity of SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79% and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial cell line 16HBE cells significantly increased the efficiency of B[a]P-induced cell transformation. CONCLUSIONS: The present data shows for the first time that decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human bronchial epithelial cell transformation, and might serve as a novel potential biomarker for early detection of LSCC.

  12. Genotoxic and carcinogenic risks associated with the dietary consumption of repeatedly heated coconut oil.

    Science.gov (United States)

    Srivastava, Smita; Singh, Madhulika; George, Jasmine; Bhui, Kulpreet; Murari Saxena, Anand; Shukla, Yogeshwer

    2010-11-01

    Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeated heating of edible oils can generate a number of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported to have carcinogenic potential. Consumption of these repeatedly heated oils can pose a serious health hazard. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly heated coconut oil (RCO), which is one of the commonly consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO, single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH, known to possess carcinogenic potential, in RCO when compared with SCO. Oral intake of RCO in Wistar rats resulted in a significant induction of aberrant cells (P<0·05) and micronuclei (P<0·05) in a dose-dependent manner. Oxidative stress analysis showed a significant (P<0·05) decrease in the levels of antioxidant enzymes such as superoxide dismutase and catalase with a concurrent increase in reactive oxygen species and lipid peroxidation in the liver. In addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci as noticed by alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific biomarkers. A significant decrease in the relative and absolute hepatic weight of RCO-supplemented rats was recorded (P<0·05). In conclusion, dietary consumption of RCO can cause a genotoxic and preneoplastic change in the liver.

  13. A simple procedure for estimating pseudo risk ratios from exposure to non-carcinogenic chemical mixtures.

    Science.gov (United States)

    Scinicariello, Franco; Portier, Christopher

    2016-03-01

    Non-cancer risk assessment traditionally assumes a threshold of effect, below which there is a negligible risk of an adverse effect. The Agency for Toxic Substances and Disease Registry derives health-based guidance values known as Minimal Risk Levels (MRLs) as estimates of the toxicity threshold for non-carcinogens. Although the definition of an MRL, as well as EPA reference dose values (RfD and RfC), is a level that corresponds to "negligible risk," they represent daily exposure doses or concentrations, not risks. We present a new approach to calculate the risk at exposure to specific doses for chemical mixtures, the assumption in this approach is to assign de minimis risk at the MRL. The assigned risk enables the estimation of parameters in an exponential model, providing a complete dose-response curve for each compound from the chosen point of departure to zero. We estimated parameters for 27 chemicals. The value of k, which determines the shape of the dose-response curve, was moderately insensitive to the choice of the risk at the MRL. The approach presented here allows for the calculation of a risk from a single substance or the combined risk from multiple chemical exposures in a community. The methodology is applicable from point of departure data derived from quantal data, such as data from benchmark dose analyses or from data that can be transformed into probabilities, such as lowest-observed-adverse-effect level. The individual risks are used to calculate risk ratios that can facilitate comparison and cost-benefit analyses of environmental contamination control strategies.

  14. Increase of carcinogenic risk via enhancement of cyclooxygenase-2 expression and hydroxyestradiol accumulation in human lung cells as a result of interaction between BaP and 17-beta estradiol.

    Science.gov (United States)

    Chang, Louis W; Chang, Yun-Ching; Ho, Chia-Chi; Tsai, Ming-Hsien; Lin, Pinpin

    2007-07-01

    Animal studies demonstrated that females are more susceptible than males to benzo[a]pyrene (BaP)-induced toxicities, including lung carcinogenesis. Elevation of cyclooxygenase-2 (COX-2) expression has been shown to increase the risk of cancer development. BaP induces COX-2 expression, and an interaction between BaP and estrogen in relation to COX-2 expression is suspected. In the present study, 10 muM BaP alone only slightly increased COX-2 mRNA expression and 10 nM 17-beta estradiol (E(2)) alone slightly increased prostaglandin E2 (PGE2) secretion in human bronchial epithelial cells. However, co-treatment with BaP and E(2) potentiated COX-2 mRNA expression and significantly elevated PGE2 secretion. Utilizing specific inhibitors and reporter assays, we further investigated the potentiation mechanisms of E(2) on BaP-induced COX-2 expression. First, E(2) activated estrogen receptor to increase PGE2 secretion, which directly increased COX-2 expression. Second, E(2) potentiated BaP-induced nuclear factor-kappaB (NF-kappaB) activation, which regulates COX-2 expression. Third, although the aryl hydrocarbon receptor (AhR) did not play a role in BaP-induced COX-2 expression, the potentiation effect of E(2) itself was AhR dependent. We further demonstrated that BaP induced the production of genotoxic E(2) metabolites (2- and 4-hydroxyestradiols) via AhR-up-regulated cytochromes P450 1A1 and 1B1. These metabolites could directly activate NF-kappaB to further promote COX-2 mRNA expression in human lung epithelial cells. These findings were further supported by increased PGE2 secretion in rat lung slice cultures. Our findings that the BaP-E(2) interaction enhanced COX-2 expression and hydroxyestradiol accumulation in the media of cultivated lung cells and tissues provide the needed scientific basis for higher risk of BaP-associated lung cancer in females.

  15. Relationship between the degree of endoscopic atrophy of the gastric mucosa and carcinogenic risk.

    Science.gov (United States)

    Masuyama, Hironori; Yoshitake, Naoto; Sasai, Takako; Nakamura, Tetsuya; Masuyama, Atsushi; Zuiki, Toru; Kurashina, Kentaro; Mieda, Mitsuyo; Sunada, Keijiro; Yamamoto, Hironori; Togashi, Kazutomo; Terano, Akira; Hiraishi, Hideyuki

    2015-01-01

    The relationship between Helicobacter pylori infection and gastric cancer has been demonstrated, and the risk of gastric cancer occurrence is known to increase with the progression of atrophic changes associated with chronic gastritis. Endoscopic evaluation of the degree and extent of atrophy of the gastric mucosa is a simple and very important means of identifying a group at high risk for gastric cancer. This study aimed to clarify the carcinogenic risk in relation to the degree of atrophy. A total of 27,777 patients (272 with early gastric cancer and 135 with advanced gastric cancer) were included in this study. Endoscopically evaluated atrophy of the gastric mucosa was classified as C-0 to O-3 according to the Kimura and Takemoto classification system. The cancer detection rate in relation to the degree of gastric mucosal atrophy was 0.04% (2/4,183 patients) for C-0, 0% (0/4,506) for C-1, 0.25% (9/3,660) for C-2, 0.71% (21/2,960) for C-3, 1.32% (75/5,684) for O-1, 3.70% (140/3,780) for O-2 and 5.33% (160/3,004) for O-3. As to the proportions of differentiated and undifferentiated cancers, the latter were relatively frequent in the C-0 to C-2 groups, but differentiated cancers became predominant as atrophy progressed. On the other hand, the number of both differentiated and undifferentiated cancers detected increased as gastric mucosal atrophy progressed. In addition, open-type atrophy was found in 29 (96.7%) of 30 patients with synchronous multiple gastric cancers and in all 20 patients with metachronous multiple gastric cancers. Endoscopic evaluation of gastric mucosal atrophy can provide a simple and reliable predictive index for both current and future carcinogenic risk. © 2015 S. Karger AG, Basel.

  16. Non-carcinogenic risk assessment of eight metals in the source groundwater of Shaying River basin.

    Science.gov (United States)

    Ni, Tian-hua; Diao, Wei-ping; Xu, Jian-gang; Liu, Ning

    2011-07-01

    Because of serious pollution of river water, people living along the Shaying River in China exploit the groundwater as a drinking water resource. Various pollutants including heavy metals have been detected in the groundwater at depths up to 200 m. To perform a non-carcinogenic risk assessment, the hazard index (HI) was determined for several metals present in the groundwater. High resolution inductively coupled plasma-mass spectrometry and inductively coupled plasma-atomic emission spectroscopy were used to measure the levels of Hg, Fe, Mn, Zn, Cd, Cr, Cu and Pb in source groundwater of eight tap water treatment plants (WTPs) during a 3-year period (2007-2009). Zn was present at the highest concentration of up to 101.2 μg l(-1) and Cd contributed the most (57.8%) to the HI in the WTPs, followed by Mn (14.3%) and Cr (13.1%). Both hazard quotients of individual metals and HI of total non-carcinogenic risk in each WTP were below 1.0, suggesting that the water posed negligible health risk on local residents. Temporal and spatial comparisons showed that high HIs tend to occur in low water periods (i.e., summer), and the City Pressure Station (Fuyang City) had the highest HI, followed by Yingnan Pressure Station (Yingnan Country) and Taihe WTP (Taihe Country). This study provides benchmark information useful for regulatory authorities to control the discharge of metals into the Shaying River Basin, and serves as a basis for comparison to other river systems in the world.

  17. The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences.

    Science.gov (United States)

    vom Brocke, Jochen; Krais, Annette; Whibley, Catherine; Hollstein, Monica C; Schmeiser, Heinz H

    2009-01-01

    3-Nitrobenzanthrone (3-NBA) is a potent mutagen and a suspected human carcinogen present in particulate matter of diesel exhaust and ambient air pollution. Employing an assay with human p53 knock-in (Hupki) murine embryonic fibroblasts (HUFs), we examined p53 mutations induced by 3-NBA and its active metabolite, N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA). Twenty-nine immortalized cultures (cell lines) from 89 HUF primary cultures exposed at passage 1 for 5 days to 2 microM 3-NBA harboured 22 different mutations in the human DNA-binding domain sequence of the Hupki p53 tumour suppressor gene. The most frequently observed mutation was GC to TA transversion (46%), corroborating previous mutation studies with 3-NBA, and consistent with the presence of persistent 3-NBA-guanosine adducts found in DNA of exposed rodents. Six of the transversions found solely in 3-NBA-treated HUFs have not been detected thus far in untreated HUFs, but have been found repeatedly in human lung tumours. (32)P-post-labelling adduct analysis of DNA from HUF cells treated with 2 microM 3-NBA for 5 days showed a pattern similar to that found in vivo, indicating the metabolic competence of HUF cells to metabolize 3-NBA to electrophilic intermediates. Total DNA binding was 160 +/- 56 per 10(7) normal nucleotides with N(2)-guanosine being the major adduct. In contrast, identical treatment with N-OH-3-ABA resulted in a 100-fold lower level of specific DNA adducts and no carcinogen-specific mutation pattern in the Hupki assay. This indicates that the level of DNA adduct formation by the mutagen is critical to obtain specific mutation spectra in the assay. Our results are consistent with previous experiments in Muta Mouse and are compatible with the possibility that diesel exhaust exposure contributes to mutation load in humans and to lung cancer risk.

  18. Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

    Science.gov (United States)

    Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

    2013-07-01

    The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship.

  19. Human gastric cancer, Helicobacter pylori and bracken carcinogens: A connecting hypothesis.

    Science.gov (United States)

    Oliveros-Bastidas, Alberto; Calcagno-Pissarelli, María Pía; Naya, Marlene; Ávila-Núñez, Jorge Luis; Alonso-Amelot, Miguel E

    2016-03-01

    Long term infection of Helicobacter pylori (Hp) virulent strains is a key factor in the genesis of human gastric cancer, and so are certain dietary proinflammatory and genotoxic compounds. Carcinogenic bracken fern (Pteridium spp.) is one of these. Toxins from this plant are consumed as bracken culinary preparations, through milk and meat of bracken-exposed livestock, and drain waters from bracken swards. Bracken toxin ptaquiloside (PtQ), a suspected human carcinogen, elicits complex responses in animals leading to death. PtQ and Hp might cooperate in gastric pathologies. This paper presents an hypothesis on PtQ-Hp association leading to the enhancement of carcinogenesis in the human gastric environment that might explain the high gastric cancer incidence and death rates among Hp-infected people living in bracken zones at two levels: (1) The macroscopic scale comprising the flow of PtQ in the human diet. (2) the microscopic scale encompassing (A) gastric luminal medium; (B) gastric mucus structure and mucin degradation elicited by Hp; (C) bacterial pH gradient modification of the gastric mucosa that favors PtQ survival and its penetration into epithelial tissue; (D) combined PtQ/Hp effects on gastric immune and inflammatory responses; (E) PtQ-Hp complementary activity at selected cell signaling cascades and genome disturbance.

  20. KEYNOTE LECTURES-KL1 New development in risk assessment of genotoxic carcinogens in foods

    Institute of Scientific and Technical Information of China (English)

    CHEN Jun-Shi

    2006-01-01

    @@ The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.

  1. 78 FR 68849 - Draft Current Intelligence Bulletin “Update of NIOSH Carcinogen Classification and Target Risk...

    Science.gov (United States)

    2013-11-15

    ... consistent with the current scientific knowledge of toxicology, risk assessment, industrial hygiene, and... there additional scientific information related to the issues of the proposed NIOSH carcinogen policies...) where clarification is needed. (7) An analytical feasibility (AF) notation will be used to identify...

  2. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    OpenAIRE

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  3. Polycyclic aromatic hydrocarbons (PAHs) in the settled dust of automobile workshops, health and carcinogenic risk evaluation.

    Science.gov (United States)

    Ali, Nadeem; Ismail, Iqbal Mohammad Ibrahim; Khoder, Mamdouh; Shamy, Magdy; Alghamdi, Mansour; Al Khalaf, Abdulrahman; Costa, Max

    2017-12-01

    There are studies available on the occurrence of PAHs in indoor settled dust from residential and different occupational settings in literature but limited data is available on their occurrence and potential health risk assessment in automobile workshops. In recent decades Saudi Arabia has experienced tremendous growth in the petroleum industry and as a result, the automobile industry is booming. People working in automobile workshops are at a greater risk of exposure to chemicals releasing from the petroleum products. The main objective of this study was to report PAHs in settled dust from different automobile workshops of Jeddah, Saudi Arabia, and evaluate health risk for workers through dust exposure. Pyrene (1585-13500ng/g), Benz[a]anthracene (risk assessment was calculated based on benzo[a]pyrene equivalent carcinogenic power (BaPE), incremental lifetime cancer risk (ILCR), and daily exposure to PAHs via dust ingestion. The median concentration of BaPE was 285ng/g, ILCR was up to 6.78×10(-3) (exceeded reference values of USEPA (range between 1×10(-6) and 1×10(-4))), and worker's exposure via dust ingestion on daily bases reached up to 33ng/kgbw/day for ∑12PAHs. This study showed people working in automobile workshops in the studied area are getting expose to high levels of PAHs via dust ingestion, inhalation, and dermal contact. This is the first study reporting PAHs in automobile workshops settings from Middle East. The incremental lifetime cancer risk to workers via dust exposure exceeded set limits of USEPA. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Computation of thyroid doses and carcinogenic radiation risks to patients undergoing neck CT examinations.

    Science.gov (United States)

    Huda, Walter; Spampinato, Maria V; Tipnis, Sameer V; Magill, Dennise

    2013-10-01

    The aim of the study was to investigate how differences in patient anatomy and CT technical factors in neck CT impact on thyroid doses and the corresponding carcinogenic risks. The CTDIvol and dose-length product used in 11 consecutive neck CT studies, as well as data on automatic exposure control (AEC) tube current variation(s) from the image DICOM header, were recorded. For each CT image that included the thyroid, the mass equivalent water cylinder was estimated based on the patient cross-sectional area and average relative attenuation coefficient (Hounsfield unit, HU). Patient thyroid doses were estimated by accounting for radiation intensity at the location of the patient's thyroid, patient size and the scan length. Thyroid doses were used to estimate thyroid cancer risks as a function of patient demographics using risk factors in BEIR VII. The length of the thyroid glands ranged from 21 to 54 mm with an average length of 42 ± 12 mm. Water cylinder diameters corresponding to the central slice through the patient thyroid ranged from 18 to 32 cm with a mean of 25 ± 5 cm. The average CTDIvol (32-cm phantom) used to perform these scans was 26 ± 6 mGy, but the use of an AEC increased the tube current by an average of 44 % at the thyroid mid-point. Thyroid doses ranged from 29 to 80 mGy, with an average of 55 ± 19 mGy. A 20-y-old female receiving the highest thyroid dose of 80 mGy would have a thyroid cancer risk of nearly 0.1 %, but radiation risks decreased very rapidly with increasing patient age. The key factors that affect thyroid doses in neck CT examinations are the radiation intensity at the thyroid location and the size of the patient. The corresponding patient thyroid cancer risk is markedly influenced by patient sex and age.

  5. Moving Forward in Human Cancer Risk Assessment

    OpenAIRE

    Paules, Richard S.; Aubrecht, Jiri; Corvi, Raffaella; Garthoff, Bernward; Kleinjans, Jos C.

    2010-01-01

    Background The current safety paradigm for assessing carcinogenic properties of drugs, cosmetics, industrial chemicals, and environmental exposures relies mainly on in vitro genotoxicity testing followed by 2-year rodent bioassays. This testing battery is extremely sensitive but has low specificity. Furthermore, rodent bioassays are associated with high costs, high animal burden, and limited predictive value for human risks. Objectives We provide a response to a growing appeal for a paradigm ...

  6. Swedish review strengthens grounds for concluding that radiation from cellular and cordless phones is a probable human carcinogen.

    Science.gov (United States)

    Davis, Devra Lee; Kesari, Santosh; Soskolne, Colin L; Miller, Anthony B; Stein, Yael

    2013-04-01

    With 5.9 billion reported users, mobile phones constitute a new, ubiquitous and rapidly growing exposure worldwide. Mobile phones are two-way microwave radios that also emit low levels of electromagnetic radiation. Inconsistent results have been published on potential risks of brain tumors tied with mobile phone use as a result of important methodological differences in study design and statistical power. Some studies have examined mobile phone users for periods of time that are too short to detect an increased risk of brain cancer, while others have misclassified exposures by placing those with exposures to microwave radiation from cordless phones in the control group, or failing to attribute such exposures in the cases. In 2011, the World Health Organization, International Agency for Research on Cancer (IARC) advised that electromagnetic radiation from mobile phone and other wireless devices constitutes a "possible human carcinogen," 2B. Recent analyses not considered in the IARC review that take into account these methodological shortcomings from a number of authors find that brain tumor risk is significantly elevated for those who have used mobile phones for at least a decade. Studies carried out in Sweden indicate that those who begin using either cordless or mobile phones regularly before age 20 have greater than a fourfold increased risk of ipsilateral glioma. Given that treatment for a single case of brain cancer can cost between $100,000 for radiation therapy alone and up to $1 million depending on drug costs, resources to address this illness are already in short supply and not universally available in either developing or developed countries. Significant additional shortages in oncology services are expected at the current growth of cancer. No other environmental carcinogen has produced evidence of an increased risk in just one decade. Empirical data have shown a difference in the dielectric properties of tissues as a function of age, mostly due to the

  7. OVERVIEW OF DRINKING WATER MUTAGENICITY AND CARCINOGENICITY AND RISK FOR BLADDER CANCER

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroacetic acid and chlorite) are not carcinogenic-in either of 2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxici...

  8. Aflatoxin is not a probably human carcinogen: the published evidence is sufficient.

    Science.gov (United States)

    Stoloff, L

    1989-12-01

    Since the early 1960s, when aflatoxin, the mold-produced contaminant of a number of important food commodities, was found to be a potent hepatocarcinogen for laboratory rats, there has been a sustained search for evidence to support the regulatory presumption that aflatoxin is a probable human carcinogen. The developing laboratory evidence of differences between species in metabolism of aflatoxin and susceptibility to its oncogenic effects indicated that humans were probably refractory to aflatoxin carcinogenesis, but the early epidemiological evidence indicated otherwise. That epidemiological evidence, however, contained flaws so that Working Groups of the International Agency for Research on Cancer (IARC) meeting in 1970, 1976, and 1982, although ignoring the biochemical evidence, did consider the available epidemiological evidence insufficient for a conclusion of human carcinogenicity. During the 1970s and 1980s, studies on the connection between chronic infection with hepatitis B virus (HBV) and primary liver cell cancer (PLC), the expected lesion from aflatoxin exposure, had established a very strong etiological relationship between HBV and PLC. Since all the epidemiological studies of aflatoxin and PLC conducted prior to 1982 had been of populations with endemic HBV infection, and, in addition to other flaws, had not been controlled for this confounding factor, there was a solid basis for their rejection. Most epidemiological studies in the 1980s of aflatoxin and PLC were either in the United States, where HBV-infected groups could be excluded from the study, or, when in areas of chronic HBV infection, attempts were made to include that factor. The study of U.S. populations showed no difference in mortality rates from PLC that could be attributed to aflatoxin exposure. The studies of populations with endemic HBV infection produced no convincing evidence to support a primary role for aflatoxin in the induction of human PLC, although an accessory role to HBV

  9. Evaluation of the potential carcinogenicity of chlorambucil. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1988-06-01

    Chlorambucil is a probable human carcinogen, classified as weight-of-evidence Group B1 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Limited. Data available are inadequate for calculating a potency factor (F) and no quantitative inferences can be made according to the CAG's methodology for evaluating potential carcinogens. Chlorambucil is, therefore, assigned to the median potency factor range and placed in potency group 2. Combining the weight-of-evidence group and the potency group, chlorambucil is assigned a MEDIUM hazard ranking.

  10. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    Science.gov (United States)

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  11. FTIR analysis and evaluation of carcinogenic and mutagenic risks of nitro-polycyclic aromatic hydrocarbons in PM1.0.

    Science.gov (United States)

    Schneider, Ismael Luís; Teixeira, Elba Calesso; Agudelo-Castañeda, Dayana Milena; Silva e Silva, Gabriel; Balzaretti, Naira; Braga, Marcel Ferreira; Oliveira, Luís Felipe Silva

    2016-01-15

    Nitro-polycyclic aromatic hydrocarbons (NPAHs) represent a group of organic compounds of significant interest due to their presence in airborne particulates of urban centers, wide distribution in the environment, and mutagenic and carcinogenic properties. These compounds, associated with atmospheric particles of size mutagenic risks of the studied NPAHs associated with PM1.0 samples were also determined for two sampling sites: Canoas and Sapucaia do Sul. The results showed that NPAH standard spectra can effectively identify NPAHs in PM1.0 samples. The transmittance and emissivity sample spectra showed broader bands and lower relative intensity than the standard NPAH spectra. The carcinogenic risk and the total mutagenic risk were calculated using the toxic equivalent factors and mutagenic potency factors, respectively. Canoas showed the highest total carcinogenic risk, while Sapucaia do Sul had the highest mutagenic risk. The seasonal analysis suggested that in the study area the ambient air is more toxic during the cold periods. These findings might of significant importance for the decision and policy making authorities.

  12. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    Directory of Open Access Journals (Sweden)

    Mette Mogensen

    2010-10-01

    Full Text Available Mette Mogensen1, Gregor BE Jemec21Department of Dermatology, Gentofte Hospital, Hellerup, Denmark; 2Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, DenmarkIntroduction: In 2009, the WHO listed ultraviolet (UV radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice.Methods: A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers.Results: Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior.Discussion: The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers.Keywords: tanning beds, skin cancers, melanoma, nonmelanoma

  13. The commuters' exposure to volatile chemicals and carcinogenic risk in Mexico City

    Science.gov (United States)

    Shiohara, Naohide; Fernández-Bremauntz, Adrián A.; Blanco Jiménez, Salvador; Yanagisawa, Yukio

    The commuters' exposure levels to volatile organic compounds were investigated in the following public transport modes: private car, microbus, bus, and metro along three commuting routes in the Metropolitan Area of Mexico City. The target chemicals were benzene, toluene, ethylbenzene, m/ p-xylene, and formaldehyde. Integrated samples were taken while traveling during the morning rush hour (weekdays 7:00-9:00 a.m.) for six consecutive weeks in June and July, 2002. Scheffe test showed that the average concentrations of all chemicals inside cars and microbuses were statistically higher than in metro trains ( Ptransport routes. These findings suggest that for commuting trips of comparable durations, car and microbus passengers are exposed to higher levels of volatile organic compounds than bus and metro commuters. These findings are consistent with previous studies looking at exposure of commuters to carbon monoxide. The lifetime carcinogenic risk from commuting by car was 2.0×10 -5-3.1×10 -5, that by microbus was 3.1×10 -5-4.0×10 -5, that by bus was 2.0×10 -5-2.7×10 -5, and that by metro was 1.3×10 -5-1.7×10 -5 in Mexico City.

  14. Human cytochrome P450 enzyme specificity for bioactivation of safrole to the proximate carcinogen 1′-hydroxysafrole

    NARCIS (Netherlands)

    Jeurissen, S.M.F.; Bogaards, J.J.P.; Awad, H.M.; Boersma, M.G.; Brand, W.; Fiamegos, Y.C.; Beek, T.A. van; Alink, G.M.; Sudhölter, E.J.R.; Cnubben, N.H.P.; Rietjens, I.M.C.M.

    2004-01-01

    In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1′-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1′-hydroxylation of safrole was characterized in a variety of in vitro te

  15. Human Cytochrome P450 Enzymes of Importance for the Bioactivation of Methyleugenol to the Proximate Carcinogen 1'-Hydroxymethyleugenol

    NARCIS (Netherlands)

    Jeurissen, S.M.F.; Bogaards, J.J.P.; Boersma, M.G.; Horst, ter J.P.F.; Awad, H.M.; Fiamegos, Y.C.; Beek, van T.A.; Alink, G.M.; Sudhölter, E.J.R.; Cnubben, N.H.P.; Rietjens, I.M.C.M.

    2006-01-01

    In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1'-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19,

  16. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    NARCIS (Netherlands)

    Kuempel, Eileen D; Jaurand, Marie-Claude; Møller, Peter; Morimoto, Yasuo; Kobayashi, Norihiro; Pinkerton, Kent E; Sargent, Linda M; Vermeulen, Roel C H; Fubini, Bice; Kane, Agnes B

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the

  17. Changes in expression of imprinted genes following treatment of human cancer cell lines with non-mutagenic or mutagenic carcinogens.

    Science.gov (United States)

    Shibui, Takeo; Higo, Yukari; Tsutsui, Takeo W; Uchida, Minoru; Oshimura, Mitsuo; Barrett, J Carl; Tsutsui, Takeki

    2008-08-01

    It remains possible that chemicals that act by mutagenic mechanisms as well as chemicals that do not induce gene mutations may affect epigenetic gene expression. To test the possibility, we investigated the ability of both types of chemicals to alter the expression of five imprinted genes, PEG3, SNRPN, NDN, ZAC and H19, using two human colon cancer cell lines and a human breast cancer cell line. The expression of imprinted genes was changed by some non-mutagenic and mutagenic carcinogens independent of their mutagenic activity. The genes most commonly exhibiting the changes in expression were SNRPN and PEG3. Alterations of the expression of NDN and ZAC were also observed in some conditions. Methylation-specific PCR and chromatin immunoprecipitation assays suggest the possibility that changes in the expression of SNRPN may be associated with DNA hypomethylation and histone acetylation of the promoters and euchromatinization of the heterochromatic domains of the promoters. Changes in expression of the imprinted genes, PEG3 and NDN, were also observed in cells immortalized by treatment of normal human fibroblasts with 4-nitroquinoline 1-oxide or aflatoxin B1. We previously demonstrated that expression of the cancer-related gene, INK4a, in these immortal cells was lost via epigenetic mechanisms. The results prove that, in cancer cells, some mutagenic or non-mutagenic carcinogens can epigenetically influence the transcription levels of imprinted genes and also suggest the possibility that some chemical carcinogens may have epigenetic carcinogenic effects in human cells.

  18. Human cytochrome P450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1′-hydroxymethyleugenol

    NARCIS (Netherlands)

    Jeurissen, S.M.F.; Bogaards, J.J.P.; Boersma, M.G.; Horst, J.P.F. ter; Awad, H.M.; Fiamegos, Y.C.; Beek, T.A. van; Alink, G.M.; Sudhölter, E.J.R.; Cnubben, N.H.P.; Rietjens, I.M.C.M.

    2006-01-01

    In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1′-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19,

  19. Chemoprevention with Acetylsalicylic Acid, Vitamin D and Calcium Reduces Risk of Carcinogen-induced Lung Tumors

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, J

    2013-01-01

    Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor.......Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor....

  20. Human health risk assessment for silver catfish Schilbe intermedius ...

    African Journals Online (AJOL)

    2014-09-03

    Sep 3, 2014 ... such as metals and pesticides (Dudgeon et al., 2006; Strayer and Dudgeon ... fish, piscivorous birds, mammals and humans (Chapman and. Wang, 2000). .... Risk assessments evaluating non-carcinogenic toxic effects of contaminants use ..... AL-KAHTANI MA (2009) Accumulation of heavy metals in tilapia.

  1. Chemoprevention with Acetylsalicylic Acid, Vitamin D and Calcium Reduces Risk of Carcinogen-induced Lung Tumors

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, J

    2013-01-01

    Background/Aim: Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor....

  2. Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Ruano-Ravina, Alberto, E-mail: alberto.ruano@usc.es [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); CIBER de Epidemiología y Salud Pública CIBERESP, Barcelona (Spain); García-Lavandeira, José Antonio [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); Department of Preventive Medicine, A Coruña University Hospital Complex, Coruña (Spain); Torres-Durán, María [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); Service of Neumology, University Hospital Complex of Vigo, Vigo (Spain); Prini-Guadalupe, Luciana [Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela (Spain); Parente-Lamelas, Isaura [Service of Neumology, Ourense Hospital Complex, Ourense (Spain); Leiro-Fernández, Virginia [Service of Neumology, University Hospital Complex of Vigo, Vigo (Spain); Montero-Martínez, Carmen [Service of Neumology, University Hospital Complex of A Coruña, Coruña (Spain); González-Barcala, Francisco Javier; Golpe-Gómez, Antonio [Service of Neumology, Santiago de Compostela University Clinic Hospital, Santiago de Compostela (Spain); Martínez, Cristina [National Institute of Silicosis, University Hospital of Asturias, Oviedo, Asturias (Spain); Castro-Añón, Olalla [Service of Neumology, Hospital Lucus Augusti, Lugo (Spain); Mejuto-Martí, María José [Service of Neumology, Hospital Arquitecto Marcide, Ferrol (Spain); and others

    2014-07-15

    We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78–2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93–5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. - Highlights: • Some leisure time activities are associated with the exposure to carcinogenic substances. • These activities are model-making, painting (artistic or not), furniture refinishing or wood working. • Few studies have assessed lung cancer risk due to these hobbies and none in never-smokers. • Leisure activities related to exposure to carcinogenic substances present higher lung cancer risk. • The risk is higher when these activities are performed for more than 10 years.

  3. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    Directory of Open Access Journals (Sweden)

    Brophy James T

    2012-11-01

    Full Text Available Abstract Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration. Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82; bars-gambling (OR = 2.28; 95% CI, 0.94-5.53; automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88, food canning (OR = 2.35; 95% CI, 1.00-5.53, and metalworking (OR = 1.73; 95% CI, 1.02-2.92. Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4 and food canning (OR = 5.70; 95% CI, 1.03-31.5. Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and

  4. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    Science.gov (United States)

    2012-01-01

    Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5). Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and

  5. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study.

    Science.gov (United States)

    Brophy, James T; Keith, Margaret M; Watterson, Andrew; Park, Robert; Gilbertson, Michael; Maticka-Tyndale, Eleanor; Beck, Matthias; Abu-Zahra, Hakam; Schneider, Kenneth; Reinhartz, Abraham; Dematteo, Robert; Luginaah, Isaac

    2012-11-19

    Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case-control design, exposure effects were estimated using conditional logistic regression. Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5). These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work

  6. Carcinogenic polycyclic aromatic hydrocarbons in umbilical cord blood of human neonates from Guiyu, China

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yongyong; Huo, Xia [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Wu, Kusheng [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Department of Preventive Medicine, Shantou University Medical College, Shantou (China); Liu, Junxiao; Zhang, Yuling [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou (China)

    2012-06-15

    Unregulated electronic-waste recycling results in serious environmental pollution of polycyclic aromatic hydrocarbons (PAHs) in Guiyu, China. We evaluated the body burden of seven carcinogenic PAHs and potential health risks for neonates. Umbilical cord blood (UCB) samples were collected from Guiyu (n = 103), and the control area of Chaonan (n = 80), China. PAHs in UCB were determined by gas chromatography/mass spectrometry. The median N-Ary-Summation 7c-PAH concentration was 108.05 ppb in UCB samples from Guiyu, vs. 79.36 ppb in samples from Chaonan. Residence in Guiyu and longer cooking time of food during the gestation period were significant factors contributing to the N-Ary-Summation 7c-PAH level. Benzo[a]anthracene (BaA), chrysene (Chr), and benzo[a]pyrene (BaP) were found to correlate with reduced neonatal height and gestational age. Infants experiencing adverse birth outcomes, on the whole, displayed higher BaA, Chr, and BaP levels compared to those with normal outcomes. We conclude that maternal PAH exposure results in fetal accumulation of toxic PAHs, and that such prenatal exposure correlates with adverse effects on neonatal health.

  7. Carcinogenic compounds in alcoholic beverages: an update.

    Science.gov (United States)

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

  8. Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.

    Science.gov (United States)

    Rao, C V; Desai, D; Kaul, B; Amin, S; Reddy, B S

    1992-11-16

    Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems.

  9. The human immune system's response to carcinogenic and other infectious agents transmitted by mosquito vectors.

    Science.gov (United States)

    Johansson, Olle; Ward, Martin

    2017-01-01

    It has been hypothesised that mosquitoes [Diptera: Culicidae] may play more of a role in certain cancers than is currently appreciated. Research links 33 infectious agents to cancer, 27 of which have a presence in mosquitoes, and that, in addition, mosquito saliva downregulates the immune system. The objective of this paper is to review the literature on the immune system and cancer-causing infectious agents, particularly those present in mosquitoes, with a view to establishing whether such infectious agents can, in the long run, defeat the immune system or be defeated by it. Many of the viruses, bacteria and parasites recognised by the International Agency for Research on Cancer (IARC) as carcinogenic and suspected by others as being involved in cancer have evolved numerous complex ways of avoiding, suppressing or altering the immune system's responses. These features, coupled with the multiplicity and variety of serious infectious agents carried by some species of mosquitoes and the adverse effects on the immune system of mosquito saliva, suggest that post-mosquito bite the immune system is likely to be overwhelmed. In such a situation, immunisation strategies offer little chance of cancer prevention, unless a single or limited number of critical infectious agents can be isolated from the 'mosquito' cocktail. If that proves to be impossible cancer prevention will, therefore, if the hypothesis proves to be correct, rest on the twin strategies of environmentally controlling the mosquito population and humans avoiding being bitten. The latter strategy will involve determining the factors that demark those being bitten from those that are not.

  10. A cross-sectional study of a prototype carcinogenic human papillomavirus E6/E7 messenger RNA assay for detection of cervical precancer and cancer.

    Science.gov (United States)

    Castle, Philip E; Dockter, Janel; Giachetti, Cristina; Garcia, Francisco A R; McCormick, Mary Kay; Mitchell, Amy L; Holladay, E Blair; Kolk, Daniel P

    2007-05-01

    To evaluate carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 mRNA detection on clinical specimens to identify women with cervical precancer and cancer. We evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens (n=531), masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay. We found an increasing likelihood of testing positive for carcinogenic HPV E6/E7 mRNA with increasing severity of cytology (P(Trend) E6/E7 mRNA. Overall, fewer specimens tested positive for carcinogenic HPV E6/E7 mRNA than for carcinogenic HPV DNA (PE6/E7 mRNA improved the association of positive test results with cervical precancer and cancer by reducing the number of test positives in women without precancer without reducing clinical sensitivity for cervical precancer and cancer compared with detection of carcinogenic HPV E6/E7 mRNA using a lower positive cutpoint by the same assay and with detection of carcinogenic HPV DNA. We found that carcinogenic HPV E6/E7 mRNA is a potentially useful biomarker for detection of cervical precancer and cancer and warrants further evaluation.

  11. Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[def,p]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry.

    Science.gov (United States)

    Madeen, Erin P; Ognibene, Ted J; Corley, Richard A; McQuistan, Tammie J; Henderson, Marilyn C; Baird, William M; Bench, Graham; Turteltaub, Ken W; Williams, David E

    2016-10-17

    Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in nonsmokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a microdose (29 ng; 5 nCi) of [(14)C]-DBC by accelerator mass spectrometry (AMS) analysis of total [(14)C] in plasma and urine. In the current study, we utilized a novel "moving wire" interface between ultraperformance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [(14)C] product identified in plasma was unmetabolized [(14)C]-DBC itself (Cmax = 18.5 ±15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [(14)C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ±1.3 fg/mL, Tmax= 1.8 h). Several minor species of [(14)C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [(14)C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax = 6-12 h pool). [(14)C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax = 29.4 ± 11.6 pg/pool, Tmax = 6-12 h pool). Parent [(14)C]-DBC was not detected in urine. This is the first data set to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

  12. A review of human carcinogens - Part E: tobacco, areca nut, alcohol, coal smoke, and salted fish

    Energy Technology Data Exchange (ETDEWEB)

    Secretan, B.; Straif, K.; Baan, R.; Grosse, Y.; El Ghissassi, F.; Bouvard, V.; Benbrahim-Tallaa, L.; Guha, N.; Freeman, C.; Galichet, L.; Cogliano, V. [International Agency for Research on Cancer, Lyon (France)

    2009-11-15

    In October, 2009, 30 scientists from 10 countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity of tobacco, areca nut, alcohol, coal smoke, and salt-preserved fish, and to identify additional tumor sites and mechanisms of carcinogenesis. These assessments will be published as Part E of Volume 100 of the IARC Monographs.

  13. Environmental carcinogenic polycyclic aromatic hydrocarbons in soil from Himalayas, India: Implications for spatial distribution, sources apportionment and risk assessment.

    Science.gov (United States)

    Devi, Ningombam Linthoingambi; Yadav, Ishwar Chandra; Shihua, Qi; Dan, Yang; Zhang, Gan; Raha, Priyankar

    2016-02-01

    The Indian Himalayan Region (IHR) is one of the important mountain ecosystems among the global mountain system which support wide variety of flora, fauna, human communities and cultural diversities. Surface soil samples (n = 69) collected from IHR were analysed for 16 priority polycyclic aromatic hydrocarbons (PAH) listed by USEPA. The ∑16PAH concentration in surface soil ranged from 15.3 to 4762 ngg(-1) (mean 458 ngg(-1)). The sum total of low molecular weight PAH (∑LMW-PAHs) (mean 74.0 ngg(-1)) were relatively lower than the high molecular weight PAH (∑HMW-PAHs) (mean 384 ngg(-1)). The concentration of eight carcinogenic PAHs (BaA, CHR, BbF, BkF, BaP, DahA, IcdP, BghiP) were detected high in mountain soil from IHR and ranged from 0.73 to 2729 ngg(-1) (mean 272 ngg(-1)). Based on spatial distribution map, high concentration of HMW- and LMW-PAHs were detected at GS1 site in Guwahati (615 and 4071 ngg(-1)), and lowest concentration of HMW-PAHs were found at IS6 in Itanagar (5.80 ngg(-1)) and LMW-PAHs at DS2 (17.3 ngg(-1)) in Dibrugarh. Total organic carbon (TOC) in mountain soil was poorly connected with ∑PAHs (r(2) = 0.072) and Car-PAHs (r(2) = 0.048), suggesting the little role of TOC in adsorption of PAHs. Isomeric ratio of PAHs showed the source of PAH contamination in IHR is mixed of petrogenic and pyrogenic origin and was affirmed by PAHs composition profile. These source apportionment results were further confirmed by principal component analysis (PCA). Eco-toxicological analysis showed the calculated TEQ for most carcinogenic PAH were 2-4 times more than the Dutch allowed limit, while TEQ of BaP was 25 times high, suggesting increasing trend of carcinogenicity of surface soil.

  14. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  15. Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells

    Science.gov (United States)

    Li, Lihua; Yang, Huanjie; Chen, Di; Cui, Cindy; Dou, Q. Ping

    2013-01-01

    The ubiquitinproteasome system is involved in various cellular processes, including transcription, apoptosis, and cell cycle. In vitro, in vivo, and clinical studies suggest the potential use of proteasome inhibitors as anticancer drugs. Cadmium (Cd) is a widespread environmental pollutant that has been classified as a human carcinogen. Recent study in our laboratory suggested that the clinically used anti-alcoholism drug disulfiram (DSF) could form a complex with tumor cellular copper, resulting in inhibition of the proteasomal chymotrypsin-like activity and induction of cancer cell apoptosis. In the current study, we report, for the first time, that DSF is able to convert the carcinogen Cd to a proteasome-inhibitor and cancer cell apoptosis inducer. Although the DSF–Cd complex inhibited the chymotrypsin-like activity of a purified 20S proteasome with an IC50 value of 32 μmol/L, this complex was much more potent in inhibiting the chymotrypsin-like activity of prostate cancer cellular 26S proteasome. Inhibition of cellular proteasome activity by the DSF–Cd complex resulted in the accumulation of ubiquitinated proteins and the natural proteasome substrate p27, which was followed by activation of calpain and induction of apoptosis. Importantly, human breast cancer MCF10DCIS cells were much more sensitive to the DSF–Cd treatment than immortalized but non-tumorigenic human breast MCF-10A cells, demonstrating that the DSF–Cd complex could selectively induce proteasome inhibition and apoptosis in human tumor cells. Our work suggests the potential use of DSF for treatment of cells with accumulated levels of carcinogen Cd. PMID:18304598

  16. Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells.

    Science.gov (United States)

    Li, Lihua; Yang, Huanjie; Chen, Di; Cui, Cindy; Dou, Q Ping

    2008-06-01

    The ubiquitin-proteasome system is involved in various cellular processes, including transcription, apoptosis, and cell cycle. In vitro, in vivo, and clinical studies suggest the potential use of proteasome inhibitors as anticancer drugs. Cadmium (Cd) is a widespread environmental pollutant that has been classified as a human carcinogen. Recent study in our laboratory suggested that the clinically used anti-alcoholism drug disulfiram (DSF) could form a complex with tumor cellular copper, resulting in inhibition of the proteasomal chymotrypsin-like activity and induction of cancer cell apoptosis. In the current study, we report, for the first time, that DSF is able to convert the carcinogen Cd to a proteasome-inhibitor and cancer cell apoptosis inducer. Although the DSF-Cd complex inhibited the chymotrypsin-like activity of a purified 20S proteasome with an IC(50) value of 32 micromol/L, this complex was much more potent in inhibiting the chymotrypsin-like activity of prostate cancer cellular 26S proteasome. Inhibition of cellular proteasome activity by the DSF-Cd complex resulted in the accumulation of ubiquitinated proteins and the natural proteasome substrate p27, which was followed by activation of calpain and induction of apoptosis. Importantly, human breast cancer MCF10DCIS cells were much more sensitive to the DSF-Cd treatment than immortalized but non-tumorigenic human breast MCF-10A cells, demonstrating that the DSF-Cd complex could selectively induce proteasome inhibition and apoptosis in human tumor cells. Our work suggests the potential use of DSF for treatment of cells with accumulated levels of carcinogen Cd.

  17. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Cells in Vitro

    Science.gov (United States)

    1982-09-07

    Chsaactariaane a/lthe Transformed C4110. essential amino acids. IX euenstial amino acida.,USAq 2.0 mM giutamine, IX vitamina , 0.2% sodium Taumor omnk in...subcutaneous injection of *&mino acids. 2.0 mM glusamine. IX vitamina , SX 10’ carcinogen-treazed or control cells ssa. 0.2% sodium bicarbonate. S iAg/ml

  18. Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polycyclic aromatic hydrocarbon

    DEFF Research Database (Denmark)

    1978-01-01

    was found in Chinese hamster V-79 cells when they were cocultivated with bronchial explants in the presence of BzaP. The proximate carcinogenic form of BzaP, the 7,8-diol [(+/-)-r7,t8-dihyroxy-7,8-dihydrobenzo[a]pyrene], was 5-fold more potent as a promutagen than the parent compound. Neither BzaP nor the 7...

  19. Molecular bio-dosimetry for carcinogenic risk assessment in survivors of Bhopal gas tragedy

    Directory of Open Access Journals (Sweden)

    Pradyumna Kumar Mishra

    2015-12-01

    Full Text Available December 2014 marked the 30th year anniversary of Bhopal gas tragedy. This sudden and accidental leakage of deadly poisonous methyl isocyanate (MIC gas instigated research efforts to understand the nature, severity of health damage and sufferings of 570 000 ailing survivors of this tragedy. In a decade-long period, our systematic laboratory investigations coupled with long-term molecular surveillance studies have comprehensively demonstrated that the risk of developing an environmental associated aberrant disease phenotype, including cancer, involves complex interplay of genomic and epigenetic reprogramming. These findings poised us to translate this knowledge into an investigative framework of “molecular biodosimetry” in a strictly selected cohort of MIC exposed individuals. A pragmatic cancer risk-assessment strategy pursued in concert with a large-scale epidemiological study might unfold molecular underpinnings of host-susceptibility and exposureresponse relationship. The challenges are enormous, but we postulate that the study will be necessary to establish a direct initiation-promotion paradigm of environmental carcinogenesis. Given that mitochondrial retrograde signaling-induced epigenetic reprogramming is apparently linked to neoplasticity, a cutting-edge tailored approach by an expert pool of biomedical researchers will be fundamental to drive these strategies from planning to execution. Validating the epigenomic signatures will hopefully result in the development of biomarkers to better protect human lives in an overburdened ecosystem, such as India, which is continuously challenged to meet population demands. Besides, delineating the mechanistic links between MIC exposure and cancer morbidity, our investigative strategy might help to formulate suitable regulatory policies and measures to reduce the overall burden of occupational and environmental carcinogenesis.

  20. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan.

    Science.gov (United States)

    Jackson, Anna Francina; Williams, Andrew; Recio, Leslie; Waters, Michael D; Lambert, Iain B; Yauk, Carole L

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2mg/kgbw) or carcinogenic (4 and 8mg/kgbw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. Crown Copyright © 2013. All rights reserved.

  1. The Weight of Evidence Does Not Support the Listing of Styrene as “Reasonably Anticipated to be a Human Carcinogen” in NTP's Twelfth Report on Carcinogens

    Science.gov (United States)

    Rhomberg, Lorenz R.; Goodman, Julie E.; Prueitt, Robyn L.

    2013-01-01

    Styrene was listed as “reasonably anticipated to be a human carcinogen” in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis—a non-genotoxic mode of action that is specific to the mouse lung—is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as “reasonably anticipated to be a human carcinogen,” and styrene should not be listed in the Report on Carcinogens. PMID:23335843

  2. Genetic polymorphisms in the tobacco smoke carcinogens detoxifying enzyme UGT1A7 and the risk of head and neck cancer.

    NARCIS (Netherlands)

    Lacko, M.; Roelofs, H.M.J.; Morsche, R.H.M. te; Voogd, A.C.; Ophuis, M.B.; Peters, W.H.M.; Manni, J.J.

    2009-01-01

    BACKGROUND: UGT1A7 is an enzyme involved in the metabolism of (pre)carcinogens present in tobacco smoke. We investigated whether genetic polymorphisms in UGT1A7, with predicted altered enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis. METHODS: Blood samples from 427

  3. Removal of probable human carcinogenic polycyclic aromatic hydrocarbons from contaminated water using molecularly imprinted polymer.

    Science.gov (United States)

    Krupadam, Reddithota J; Khan, Muntazir S; Wate, Satish R

    2010-02-01

    A molecularly imprinted polymer (MIP) adsorbent for carcinogenic polycyclic aromatic hydrocarbons (PAHs) was prepared using a non-covalent templating technique. MIP particles sized from 2 to 5 microm were synthesized in acetonitrile by using six PAHs mix as a template, methacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as the cross-linker. When compared with the non-imprinted polymer (NIP), the MIP showed an excellent affinity towards PAHs in aqueous solution with binding capacity (B(max)) of 687 microg g(-1)MIP, imprinting effect of 6, and a dissociation constant of 24 microM. The MIP exhibited significant binding affinity towards PAHs even in the presence of environmental parameters such as dissolved organic matter (COD) and total dissolved inorganic solids (TDS), suggesting that this material may be appropriate for removal of carcinogenic PAHs. The feasibility of removing PAHs from water by the MIP demonstrated using groundwater spiked with PAHs. In addition, the MIP reusability without any deterioration in performance was demonstrated at least ten repeated cycles.

  4. A paradox of cadmium: a carcinogen that impairs the capability of human breast cancer cells to induce angiogenesis.

    Science.gov (United States)

    Pacini, Stefania; Punzi, Tiziana; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco

    2009-01-01

    Cadmium, a highly persistent heavy metal, has been categorized as a human carcinogen. Even though it is known that cadmium acts as estrogens in breast cancer cells, several studies failed to demonstrate whether cadmium is a causal factor for breast cancer. The lack of a strong association between cadmium and breast cancer could be found in the antiangiogenic properties of this heavy metal, which might counteract its carcinogenic properties in the progression of breast cancer. In this study, we exposed estrogen-responsive breast cancer cells to subtoxic levels of cadmium, and we evaluated their angiogenic potential using the chick embryo chorioallantoic membrane assay. Exposure of breast cancer cells to subtoxic levels of cadmium significantly inhibited the angiogenic potential of the breast cancer cell line, suggesting the possibility that cadmium might negatively regulate the production of proangiogenic factors in breast cancer cells. Our results suggest that cadmium might exert a paradoxical effect in breast cancer: on the one hand, it could promote carcinogenesis, and, on the other hand, it could delay the onset of tumors by inhibiting breast cancer cell-induced angiogenesis.

  5. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Anna Francina, E-mail: Francina.Jackson@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada); Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6 (Canada); Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada); Recio, Leslie, E-mail: lrecio@ils-inc.com [ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Waters, Michael D., E-mail: mwaters@ils-inc.com [ILS, Inc., P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Lambert, Iain B., E-mail: Iain.Lambert@carleton.ca [Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6 (Canada); Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca [Environmental Health Science and Research Bureau, Health Canada, Ottawa K1A 0K9 (Canada)

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

  6. Carcinogenic risk of emerging persistent organic pollutant perfluorooctane sulfonate (PFOS): A proposal of classification.

    Science.gov (United States)

    Arrieta-Cortes, Ricardo; Farias, Paulina; Hoyo-Vadillo, Carlos; Kleiche-Dray, Mina

    2017-02-01

    Perfluoroalkyls are stable synthetic chemicals, able to repel oils, fats and water. These compounds have been used in the manufacturing of products such as Teflon(®), lubricants, paints, fire-fighting foams, coatings for pans, carpets, clothes, and paperboard for packaging, among others. It is believed that populations are exposed constantly to them. Its regulation in the world is under development and several controversies are in the course of litigation. One occupational study shows bladder cancer risk. This paper intends to review scientific information on the most critical perfluoroalkyl compound and proposes a procedure to get a cancer-risk categorization which PFOS can cause to populations.

  7. Science, politics, and health in the brave new world of pharmaceutical carcinogenic risk assessment: technical progress or cycle of regulatory capture?

    Science.gov (United States)

    Abraham, John; Ballinger, Rachel

    2012-10-01

    The carcinogenicity (cancer-inducing potential) of pharmaceuticals is an important risk factor for health when considering whether thousands of patients on drug trials or millions/billions of consumers in the marketplace should be exposed to a new drug. Drawing on fieldwork involving over 50 interviews and documentary research spanning 2002-2010 in Europe and the US, and on regulatory capture theory, this article investigates how the techno-regulatory standards for carcinogenicity testing of pharmaceuticals have altered since 1998. It focuses on the replacement of long-term carcinogenicity tests in rodents (especially mice) with shorter-term tests involving genetically-engineered mice (GEM). Based on evidence regarding financial/organizational control, methodological design, and interpretation of the validation and application of these new GEM tests, it is argued that regulatory agencies permitted the drug industry to shape such validation and application in ways that prioritized commercial interests over the need to protect public health. Boundary-work enabling industry scientists to define some standards of public-health policy facilitated such capture. However, as the scientific credibility of GEM tests as tools to protect public health by screening out carcinogens became inescapably problematic, a regulatory resurgence, impelled by reputational concerns, exercised more control over industry's construction and use of the tests, The extensive problems with GEM tests as public-health protective regulatory science raises the spectre that alterations to pharmaceutical carcinogenicity-testing standards since the 1990s may have been boundary-work in which the political project of decreasing the chance that companies' products are defined as carcinogenic has masqueraded as techno-science.

  8. 1,3-Propane sultone as an extremely potent human carcinogen: description of an exposed cohort in Germany.

    Science.gov (United States)

    Bolt, Hermann M; Golka, Klaus

    2012-01-01

    1,3-Propane sultone (1,3-PS) is a directly alkylating, genotoxic and carcinogenic substance. In rats, 1,3-PS induces local and systemic tumors at multiple sites, including the mammary gland, intestine, hematopoietic system, kidneys, and the central nervous system (CNS), especially in the form of gliomas. In one particular company, 1,3-PS had been manufactured in limited amounts in the 1950s and 1960s, and for a few purposes until the 1970s. The number of individuals having been in contact with the compound occupationally comprised 55 in total. Data were obtained from this group with an open question of legal compensation regarding an occupational disease. Particular emphasis was placed on malignancies occurring among the occupationally exposed persons. As cerebral gliomas are a major type of tumor induced by 1,3-PS experimentally, the occurrence of two glioblastomas among the previously exposed persons was significant. Three intestinal malignancies were recorded within the cases observed. It is also noteworthy that there was one case of a duodenal carcinoma, which is normally a rare human malignancy. Two hematopoietic/lymphatic malignancies were observed, and there was one case of a renal cell carcinoma. The types of malignancies within a group of only 55 exposed persons are surprisingly consistent with the results from rodent studies. Data clearly indicate that 1,3-PS is carcinogenic in humans. Evidence indicates that 12 cases with various neoplasms were legally compensated within the period of 1985-2010 as an occupational disease, based on the "opening clause" of § 9 (2) SGB VII of legislation in Germany.

  9. Interindividual Difference in Metabolism of Carcinogens as a Risk Factor for Breast Cancer

    Science.gov (United States)

    1999-09-01

    polymorphism capture only a fraction of the enzyme variability in at risk individuals. We therefore decided to determine expression of CYP1B1 in the breast to...cytochrome P4501B1 ( CYP1B1 ) polymorphism with steroid receptor status in breast cancer. Cancer Res. 56: 5038-5041. 10. Hanna, I.H., Roodi, N., Guengrich...patients and CYP1B1 expression is compared in specimen from cancer patients and healthy controls to establish if breast cancer patients have an increased

  10. Multicentre study for the evaluation of mutagenic/carcinogenic risk in nurses exposed to antineoplastic drugs: assessment of DNA damage.

    Science.gov (United States)

    Buschini, Annamaria; Villarini, Milena; Feretti, Donatella; Mussi, Francesca; Dominici, Luca; Zerbini, Ilaria; Moretti, Massimo; Ceretti, Elisabetta; Bonfiglioli, Roberta; Carrieri, Mariella; Gelatti, Umberto; Rossi, Carlo; Monarca, Silvano; Poli, Paola

    2013-11-01

    People who handle antineoplastic drugs, many of which classified as human carcinogens by International Agency for Research on Cancer, are exposed to low doses in comparison with patients; however, the long duration of exposure could lead to health effects. The aim of this work was to evaluate DNA damage in white blood cells from 63 nurses who handle antineoplastic drugs in five Italian hospitals and 74 control participants, using different versions of the Comet assay. Primary DNA damage was assessed by using the alkaline version of the assay on leucocytes, whereas to detect DNA oxidative damage and cryptic lesions specifically, the Comet/ENDO III assay and the Comet/araC assay were performed on leucocytes and lymphocytes, respectively. In the present study, no significant DNA damage was correlated with the work shift. The exposed population did not differ significantly from the reference group with respect to DNA primary and oxidative damage in leucocytes. Strikingly, in isolated lymphocytes treated with araC, lower data dispersion as well as a significantly lower mean value for the percentage of DNA in the comet tail was observed in exposed participants as compared with the control group (pantineoplastic drugs. Although stringent rules were adopted at national and international levels to prevent occupational exposure to antineoplastic drugs, data reported in this study support the idea that a more efficient survey on long-lasting exposures at very low concentrations is needed.

  11. Epidemiologic evidence for chloroprene carcinogenicity: review of study quality and its application to risk assessment.

    Science.gov (United States)

    Bukowski, John Arthur

    2009-09-01

    This article evaluates the quality and weight of evidence associated with epidemiologic studies of cancer among occupational cohorts exposed to chloroprene. The focus is on liver, lung, and lymphohematopoietic cancers, which had been increased in early studies. Literature searches identified eight morbidity/mortality studies covering seven chloroprene-exposed cohorts from six countries. These studies were summarized and their quality was assessed using the 10 criteria suggested by the U.S. Environmental Protection Agency. The limitations within this literature (primarily the early studies) included crude exposure assessment, incomplete follow-up, uncertain baseline rates, and uncontrolled confounding by factors such as smoking, drinking, and co-exposure to benzene and vinyl chloride. Four cohorts were studied by the same group of investigators, who reported no overall increased associations for any cancers. This four-cohort study was by far the most rigorous, having the most comprehensive exposure assessment and follow-up and the most detailed documentation. This study also contained the two largest cohorts, including an American cohort from Louisville, Kentucky, that ranked at or near the top for each of the 10 quality criteria. There was evidence of a strong healthy worker effect in the four-cohort study, which could have hidden small excess risks. Small increased risks were suggested by internal or company-specific analyses, but these were most likely caused by uncontrolled confounding and low baseline rates. Overall, the weight of evidence does not support any substantial link between chloroprene exposure and cancer, but inconsistencies and a lack of control for major confounders preclude drawing firmer conclusions.

  12. Oxidatively generated base modifications in DNA: Not only carcinogenic risk factor but also regulatory mark?

    Science.gov (United States)

    Seifermann, Marco; Epe, Bernd

    2017-06-01

    The generation of DNA modifications in cells is in most cases accidental and associated with detrimental consequences such as increased mutation rates and an elevated risk of malignant transformation. Accordingly, repair enzymes involved in the removal of the modifications have primarily a protective function. Among the well-established exceptions of this rule are 5-methylcytosine and uracil, which are generated in DNA enzymatically under controlled conditions and fulfill important regulatory functions in DNA as epigenetic marks and in antibody diversification, respectively. More recently, considerable evidence has been obtained that also 8-oxo-7,8-dihydroguanine (8-oxoG), a frequent pro-mutagenic DNA modification generated by endogenous or exogenous reactive oxygen species (ROS), has distinct roles in the regulation of both transcription and signal transduction. Thus, the activation of transcription by the estrogen receptor, NF-κB, MYC and other transcription factors was shown to depend on the presence of 8-oxoG in the promoter regions and its recognition by the DNA repair glycosylase OGG1. The lysine-specific histone demethylase LSD1, which produces H2O2 as a by-product, was indentified as a local generator of 8-oxoG in some of these cases. In addition, a complex of OGG1 with the excised free substrate base was demonstrated to act as a guanine nucleotide exchange factor (GEF) for small GTPases such as Ras, Rac and Rho, thus stimulating signal transduction. The various findings and intriguing novel mechanisms suggested will be described and compared in this review. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Aggregate human health risk assessment from dust of daily life in the urban environment of Beijing.

    Science.gov (United States)

    Xu, L Y; Shu, X

    2014-04-01

    Because of the high emissions of polycyclic aromatic hydrocarbons (PAHs) into the environment by the increasing number of vehicles in Beijing and the absorption of these PAHs onto particulates, the performance of a preliminary health risk assessment of the aggregate exposure to PAHs of urban citizens in daily life is very important. Urban dust can be used to examine the aggregation of atmospheric particulates from local pollution sources over a long time period and the direct exposure of the urban human population. The environment's correlative with clothing, dining, residing, and traveling in urban daily life was assessed using exposure-receptor-oriented analysis. The multipathway exposure model was used to simulate the lifetime exposure of a female citizen to PAHs in dust. All of the PAH concentrations in dust for each behavior and its correlative environment in Beijing were acceptable because all of the carcinogenic risks of PAHs in the dust were approximately 1.0 × 10(-6). The dominant induced carcinogenic risks in the dust were Benzo(a)pyrene and Dibenzo(a,h)anthracene. The main carcinogenic risk routes for humans were dermal contact and oral intake, which contributed on average 99.78% of the risk. Indoor risk is especially important, as the decoration and height within the building were important impact factors for carcinogenic risk induced by indoor PAHs. For people living in an urban area, a healthy lifestyle includes less decoration per room, living on a low floor, wearing a respirator, and reducing exposed skin area when traveling.

  14. Assessment of carcinogenic and non-carcinogenic risk lead in bottled water in different age groups in Bandar Abbas Ciry, Iran.

    Science.gov (United States)

    Fakhri, Yadolah; Mohseni, Seyed Mohsen; Jafarzadeh, Saeedeh; Langarizadeh, Ghazaleh; Moradi, Bigard; Zandsalimi, Yahya; Rahimizadeh, Aziz; Mirzaei, Maryam

    2015-01-23

    The presence of heavy metals such as lead in drinking water resources can be dangerous for human because of toxicity and biological accumulation. The consumption of water or food which contains lead in high concentration can lead to prevent from Hemoglobin Synthesis (Anemia) and Kidney diseases. In this present study, the researcher collected 432 samples of bottled water in the popular marks in summer and winter from the surface of Bandar Abbas. The lead concentration was measured by atomic absorption Spectrophotometer in model DR2800 through the Dithizone method. CDI, R and HQ which are caused by lead for adult men, women and children, have been calculated and evaluated through the equations of EPA and WHO. The mean concentration of lead, which is 3.46± 0.47 µg/l, and its range, which is 1.9-17.6 µg/l, are lower than the guideline of WHO (10 µg/l) and MPC of EPA is (15 µg/l). But the 40 samples of the bottled water (9.2%) have the concentration higher than guideline WHO and 8 samples (1.85%) has the concentration higher than the permissible limits of the EPA. CDI in different age groups is as following manner: Children>adult men>adult women. CDI in children is more than twice as much as in the adult men and women. The R of lead for children (24E-7), adult men (11E-7) and for adult women (10E-7) are more than the acceptable level of R in EPA (1E-6) but less than the acceptable level of R in WHO (1E-4). Since HQ of adult men (34E-5), adult women (31E-5) and children (84E-5), is lower than 1, it can be said that the population of Bandar Abbas is in a safe area regarding the HQ of the bottled water's lead.

  15. Formation of a carcinogenic aromatic amine from an azo dye by human skin bacteria in vitro.

    Science.gov (United States)

    Platzek, T; Lang, C; Grohmann, G; Gi, U S; Baltes, W

    1999-09-01

    Azo dyes represent the major class of dyestuffs. They are metabolised to the corresponding amines by liver enzymes and the intestinal microflora following incorporation by both experimental animals and humans. For safety evaluation of the dermal exposure of consumers to azo dyes from wearing coloured textiles, a possible cleavage of azo dyes by the skin microflora should be considered since, in contrast to many dyes, aromatic amines are easily absorbed by the skin. A method for measuring the ability of human skin flora to reduce azo dyes was established. In a standard experiment, 3x10(11) cells of a culture of Staphylococcus aureus were incubated in synthetic sweat (pH 6.8, final volume 20 mL) at 28 degrees C for 24 h with Direct Blue 14 (C.I. 23850, DB 14). The reaction products were extracted and analysed using HPLC. The reduction product o-tolidine (3,3'-dimethylbenzidine, OT) could indeed be detected showing that the strain used was able to metabolise DB 14 to the corresponding aromatic amine. In addition to OT, two further metabolites of DB 14 were detected. Using mass spectrometry they were identified as 3,3'-dimethyl-4-amino-4'-hydroxybiphenyl and 3, 3'-dimethyl-4-aminobiphenyl. The ability to cleave azo dyes seems to be widely distributed among human skin bacteria, as, under these in vitro conditions, bacteria isolated from healthy human skin and human skin bacteria from strain collections also exhibited azo reductase activity. Further studies are in progress in order to include additional azo dyes and coloured textiles. At the moment, the meaning of the results with regard to consumer health cannot be finally assessed.

  16. Comparative pathophysiology, toxicology, and human cancer risk assessment of pharmaceutical-induced hibernoma

    Energy Technology Data Exchange (ETDEWEB)

    Radi, Zaher, E-mail: zaher.radi@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States); Bartholomew, Phillip, E-mail: phillip.m.bartholomew@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, Eastern Point Road, Groton, CT 06340 (United States); Elwell, Michael, E-mail: michael.elwell@covance.com [Covance Laboratories, Chantilly, VA 20151 (United States); Vogel, W. Mark, E-mail: w.mark.vogel@pfizer.com [Pfizer Worldwide Research and Development, Drug Safety R and D, 1 Burtt Rd., Andover, MA 01810 (United States)

    2013-12-15

    In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernoma in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas

  17. Amelioratory effect of coenzyme Q10 on potential human carcinogen Microcystin-LR induced toxicity in mice.

    Science.gov (United States)

    Lone, Yaqoob; Bhide, Mangla; Koiri, Raj Kumar

    2017-04-01

    Microcystins are a group of cyclic heptapeptide toxins produced by cyanobacteria. More than 100 microcystin analogues have been detected, among which microcystin-LR is the most abundant and toxic variant. Present study was designed to reveal whether potential human carcinogen microcystin-LR could imbalance the glycolytic-oxidative-nitrosative status of heart, kidney and spleen of mice and also to explore the amelioratory effect of coenzyme Q10 on microcystin-LR induced toxicity. Microcystin-LR was administered at a dose of 10 μg/kg bw/day, ip for 14 days in male mice. In microcystin-LR treated mice as compared to control, significant increase in the level of lipid peroxidation, hydrogen peroxide, lactate dehydrogenase, nitric oxide with a concomitant decrease in the level of glutathione was observed, suggesting microcystin-LR induced toxicity via induction of oxidative-nitrosative-glycolytic pathway. Although several studies have evaluated numerous antioxidants but still there is no effective chemoprotectant against microcystin-LR induced toxicity. When microcystin-LR treated mice were co-administered coenzyme Q10 (10 mg/kg bw/day, im) for 14 days, it was observed that coenzyme Q10 ameliorates microcystin-LR induced toxicity via modulation of glycolytic-oxidative-nitrosative stress pathway. Thus, the results suggest that coenzyme Q10 has a potential to be developed as preventive agent against microcystin-LR induced toxicity.

  18. DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl are formed at environmental exposure levels and persist in human hepatocytes.

    Science.gov (United States)

    Nauwelaërs, Gwendoline; Bellamri, Medjda; Fessard, Valérie; Turesky, Robert J; Langouët, Sophie

    2013-09-16

    Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25-100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM-10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage

  19. Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells.

    Science.gov (United States)

    1981-11-01

    the resolution and quantitation of modified ucleosides in the urine of cancer patients would not be particularly useful for the cell culture studies...Comparison of nucleic acid catabolism by normal human fibroblasts and fibroblasts transformed with methylazoxymethyl alcohol ( MAMA ),an activated...catabolite in long-term, pulse-chase experiments. However, the kinetics of catabolism differed, in that only the MAMA -transformed cells had generated

  20. Concentrations, bioaccumulation, and human health risk assessment of organochlorine pesticides and heavy metals in edible fish from Wuhan, China.

    Science.gov (United States)

    Cui, Lili; Ge, Jing; Zhu, Yindi; Yang, Yuyi; Wang, Jun

    2015-10-01

    The objective of this study was to determine concentration and bioaccumulation of organochlorine pesticides and heavy metals in edible fish from Wuhan, China, in order to assess health risk to the human via fish consumption. Two edible fish species (Aristichthys nobilis and Hypophthalmichthys molitrix) were collected and analyzed for 11 organochlorine pesticides (OCPs) and eight heavy metals (HMs). Concentrations of ∑HCHs, ∑DDTs, and ∑OCPs in fish samples were in the range of 0.37-111.20, not detected (nd)-123.61, and 2.04-189.04 ng g(-1) (wet weight), respectively. Bioaccumulation factors (BAFs) of OCPs in bighead carp (A. nobilis) were higher than those in silver carp (H. molitrix). Concentrations of ∑HMs in bighead carp and silver carp were 352.48 and 345.20 mg kg(-1) (dw), respectively. Daily exposure of OCPs and HMs for consumers was estimated by comparing estimated daily intake (EDI) with different criteria. The results revealed that the EDIs in our study were all lower than those criteria. Target hazard quotient (THQ) and risk ratio (R) were used to evaluate non-carcinogenic and carcinogenic risks, respectively. As regard to non-carcinogenic effects of the contaminants, hazard quotients (THQ) of OCPs and HMs were both lower than 1.0, implying negligible non-carcinogenic risk via fish consumption in study area. Nevertheless, in view of carcinogenic effects of the contaminants, the total value of risk ratio (R) of OCPs was lower than the threshold of tolerable risk while the total value of risk ratio (R) of HMs was higher than the threshold of tolerable risk due to the high carcinogenic risk ratios of As and Cr, indicating high carcinogenic risks via fish consumption. The results demonstrated that HMs in edible fish from Wuhan, China, especially As and Cr required more attention than OCPs.

  1. [Levels of carcinogenic, polycyclic aromatic hydrocarbons in human and animal tissues. IIIrd communication (author's transl)].

    Science.gov (United States)

    Gräf, W; Eff, H; Schormair, S

    1975-10-01

    (1) The mean content in benzypyrene (bp) of human pulmonary tissue amounts to 0.2 mug./100 g. of dry substance. As in all other organ tissues, however, the content differs with the age of the individual: in infants, we find maximum concentrations, in the medium age groups the levels decline and rise once more with increasing age. (2) No increase in the 3,4-benzpyrene levels (average: 0.2 mug./100 g. of dry substance) will be found in tissues with high cellular proliferative activity, such as exocrine and endocrine glands (pancreas, testicles, thyroid gland, adrenals, mammary glands, as well as bone marrow). (3) In human adipose tissue, as well as in that of pork and beef, the 3,4-benzpyrene levels are found to be exceedingly low. With values of 0.1 mug./100 g, the average concentrations lie markedly below the organ tissue levels. Hence, this class of noxious substances in not stored in the adipose tissue. (4) Both in man and in animals (pig, fowl), the 3,4-benzyprene concentrations consistently exceed the average values during early postnatal life. (5) This relatively high concentration of bp in early infancy is due to exogenous factors and is not the expression of biogenous synthesis, as has been demonstrated in examinations of the environmentally influenced embryonic development of the chick. Throughout the entire development of the embryo within the hen's egg, the benzpyrene levels remain constant. Only when the chickens have been hatched out do the benzyprene levels rise significantly. Thus, the low 3,4-benzpyrene levels detected in all human and animal organ tissues prove to be the result of the interplay of exogenous environmental loading and individual capability of eliminating this substance.

  2. Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells.

    Science.gov (United States)

    Huang, Jong-Khing; Huang, Chun-Jen; Chen, Wei-Chuan; Liu, Shiuh-Inn; Hsu, Shu-Shong; Chang, Hong-Tai; Tseng, Li-Ling; Chou, Chiang-Ting; Chang, Chih-Hung; Jan, Chung-Ren

    2005-07-01

    The effect of the carcinogen safrole on intracellular Ca2+ movement and cell proliferation has not been explored previously. The present study examined whether safrole could alter Ca2+ handling and growth in human oral cancer OC2 cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at a concentration of 325 microM started to increase [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 40% by removing extracellular Ca2+, and was decreased by 39% by nifedipine but not by verapamil or diltiazem. In Ca2+-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) barely induced a [Ca2+]i rise; in contrast, addition of safrole after thapsigargin treatment induced a small [Ca2+]i rise. Neither inhibition of phospholipase C with 2 microM U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 1 microM safrole did not alter cell proliferation, but incubation with 10-1000 microM safrole increased cell proliferation by 60+/-10%. This increase was not reversed by pre-chelating Ca2+ with 10 microM of the Ca2+ chelator BAPTA. Collectively, the data suggest that in human oral cancer cells, safrole induced a [Ca2+]i rise by causing release of stored Ca2+ from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion and by inducing Ca2+ influx via nifedipine-sensitive Ca2+ entry. Furthermore, safrole can enhance cell growth in a Ca2+-independent manner.

  3. Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells.

    Science.gov (United States)

    Liu, Yao-Zhong; Zhang, Lei; Roy-Engel, Astrid M; Saito, Shigeki; Lasky, Joseph A; Wang, Guangdi; Wang, He

    2017-02-20

    The health impacts of the BP oil spill are yet to be further revealed as the toxicological effects of oil products and dispersants on human respiratory system may be latent and complex, and hence difficult to study and follow up. Here we performed RNA-seq analyses of a system of human airway epithelial cells treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, we then systemically analyzed the transcriptomic perturbations of the cells at the KEGG pathway level using two pathway-based analysis tools, GAGE (generally applicable gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results suggested a pattern of change towards carcinogenesis for the treated cells marked by upregulation of ribosomal biosynthesis (hsa03008) (p=1.97E-13), protein processing (hsa04141) (p=4.09E-7), Wnt signaling (hsa04310) (p=6.76E-3), neurotrophin signaling (hsa04722) (p=7.73E-3) and insulin signaling (hsa04910) (p=1.16E-2) pathways under the dispersant Corexit 9527 treatment, as identified by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co-expression changes for several KEGG cancer pathways, including small cell lung cancer pathway (hsa05222, p=9.99E-5), under various treatments of oil/dispersant, especially the mixture of oil and Corexit 9527. Overall, our results suggested carcinogenic effects of dispersants (in particular Corexit 9527) and their mixtures with the BP crude oil, and provided further support for more stringent safety precautions and regulations for operations involving long-term respiratory exposure to oil and dispersants.

  4. Nitrites and nitrates in the human diet: Carcinogens or beneficial hypotensive agents?

    Science.gov (United States)

    Butler, Anthony

    2015-06-05

    The presence of nitrite in the human diet was thought to constitute a hazard as secondary nitrosamines are known to cause gastric cancers. Recent publications on the physiology of serum nitrite have been consulted. Nitrite is added to some foodstuffs as an antibotulinum agent. The epidemiological evidence that nitrite causes gastric ulcers is weak. On the other hand, evidence that the presence of nitrite in serum lowers blood pressure is strong. This allows us to explain why a Tang dynasty treatment for angina, given in a Dunhuang medical manuscript, can be successful. The presence of nitrite in food is free of danger and a diet high in nitrate is beneficial to the health. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

    Science.gov (United States)

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-01-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  6. Treatment of mice with the Ah receptor agonist and human carcinogen dioxin results in altered numbers and function of hematopoietic stem cells

    OpenAIRE

    Singh, Kameshwar P.; Wyman, Amber; Casado, Fanny L.; Garrett, Russell W.; Gasiewicz, Thomas A.

    2008-01-01

    The aryl hydrocarbon receptor (AhR) mediates the carcinogenicity of a family of environmental contaminants, the most potent being 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increased incidence of lymphoma and leukemia in humans is associated with TCDD exposure. Although AhR activation by TCDD has profound effects on the immune system, precise cellular and molecular mechanisms have yet to be determined. These studies tested the hypothesis that alteration of marrow populations following treatm...

  7. Molecular expression and enzymatic characterization of thioredoxin from the carcinogenic human liver fluke Opisthorchis viverrini.

    Science.gov (United States)

    Suttiprapa, Sutas; Matchimakul, Pitchaya; Loukas, Alex; Laha, Thewarach; Wongkham, Sopit; Kaewkes, Sasithorn; Brindley, Paul J; Sripa, Banchob

    2012-03-01

    The human liver fluke, Opisthorchis viverrini, induces inflammation of the hepatobiliary system. Despite being constantly exposed to inimical oxygen radicals released from inflammatory cells, the parasite survives for years. Defense against oxidative damage can be mediated through glutathione and/or thioredoxin utilizing systems. Here, we report the molecular expression and biochemical characterization of a thioredoxin (Trx) from O. viverrini. O. viverrini Trx cDNA encoded a polypeptide of 105 amino acid residues, of molecular mass 11.63 kDa. The predicted protein has similarity to previously characterized thioredoxins with 26-51% identity. Recombinant O. viverrini Trx (Ov-Trx-1) was expressed as soluble protein in E. coli. The recombinant protein showed insulin reduction activity and supported the enzymatic function of O. viverrini thioredoxin peroxidase. Expression of Ov-Trx-1 at mRNA and protein levels was observed in all obtainable developmental stages of the liver fluke. Ov-Trx-1 was also detected in excretory-secretory products released by adult O. viverrini. Immunohistochemistry, Ov-Trx-1 was expressed in nearly all parasite tissue excepted ovary and mature sperms. Interestingly, Ov-Trx-1 was observed in the infected biliary epithelium but not in normal bile ducts. These results suggest that Ov-Trx-1 is essential for the parasite throughout the life cycle. In the host-parasite interaction aspect, Ov-Trx-1 may support thioredoxin peroxidase in protecting the parasite against damage induced by reactive oxygen species from inflammation.

  8. Overview of bioassays for mutagens, carcinogens, and teratogens

    Energy Technology Data Exchange (ETDEWEB)

    Dumont, J.N.

    1982-01-01

    Bioassays to determine the risk of health hazards of man-made chemical substances are reviewed. The standard approach to testing a substance is the tier system, consisting of three levels of testing that are increasingly complex, lengthy, and costly. The paper describes the biological basis of bioassays, identifies various assays for mutagens, carcinogens and teratogens, and explains the problems involved in extrapolating test data to human risk estimates. Future improvements in assay techniques are discussed. (CR)

  9. Cytotoxicity and chromosome aberrations in normal human oral keratinocytes induced by chemical carcinogens: Comparison of inter-individual variations.

    Science.gov (United States)

    Tsutsui, T; Kawamoto, Y; Suzuki, N; Gladen, B C; Barrett, J C

    1991-01-01

    Normal human keratinocytes from the oral cavity were cultured in vitro in serum-free medium. Cultures from different individuals were established, and the responses of the cells to different chemicals were compared. The cells, grown at clonal densities, were treated separately with an alkylating agent (N-methyl-N'-nitro-N-nitrosoguanidine; MNNG), two arsenical salts (sodium arsenate or sodium arsenite), sodium fluoride or two polyaromatic hydrocarbons (benzo[a]pyrene or 7,12-dimethylbenz[a]-anthracene). There were no significant differences in the colony-forming efficiencies (22.8 +/- 4.2%) of control (untreated) cells from five different individuals. At selected doses, each of the chemicals reduced the colony-forming efficiencies of the treated cells. The cytotoxicity of most of the chemicals did not differ significantly among cells derived from different individuals, with the exception of sodium arsenate at two doses and sodium fluoride at the highest dose tested. Induction of chromosome aberrations by MNNG, sodium arsenite, sodium arsenate and sodium flouride was analysed with cells derived from up to nine individuals. There was little difference in the inducibilities of chromosome aberrations among cultured keratinocytes from different donors. Treatment of cells from nine donors with one dose of sodium fluoride revealed a statistically significant inter-individual variation. These findings provide a model system to study the effects of carcinogens on the target cells for oral cancers. The results can be compared with findings for cells from other epithelial tissues, since the culture conditions support the growth of keratinocytes regardless of origin. Little inter-individual variation was observed in the response of oral keratinocytes to the chemicals examined.

  10. Fermented wheat aleurone induces enzymes involved in detoxification of carcinogens and in antioxidative defence in human colon cells.

    Science.gov (United States)

    Stein, Katrin; Borowicki, Anke; Scharlau, Daniel; Glei, Michael

    2010-10-01

    Dietary fibre is fermented by the human gut flora resulting mainly in the formation of SCFA, for example, acetate, propionate and butyrate. SCFA, in particular butyrate, may be important for secondary cancer prevention by inducing apoptosis and inhibiting cell growth of cancer cells, thereby inhibiting the promotion and/or progression of cancer. Furthermore, SCFA could also act on primary cancer prevention by activation of detoxifying and antioxidative enzymes. We investigated the effects of fermented wheat aleurone on the expression of genes involved in stress response and toxicity, activity of drug-metabolising enzymes and anti-genotoxic potential. Aleurone was digested and fermented in vitro to obtain samples that reflect the content of the colon. HT29 cells and colon epithelial stripes were incubated with the resulting fermentation supernatant fractions (fs) and effects on mRNA expression of CAT, GSTP1 and SULT2B1 and enzyme activity of glutathione S-transferase (GST) and catalase (CAT) were measured. Fermented aleurone was also used to study the protection against H2O2-induced DNA damage in HT29 cells. The fs of aleurone significantly induced the mRNA expression of CAT, GSTP1 and SULT2B1 (HT29) and GSTP1 (epithelial stripes), respectively. The enzyme activities of GST (HT29) and CAT (HT29, epithelial stripes) were also unambiguously increased (1.4- to 3.7-fold) by the fs of aleurone. DNA damage induced by H2O2 was significantly reduced by the fs of aleurone after 48 h, whereupon no difference was observed compared with the faeces control. In conclusion, fermented aleurone is able to act on primary prevention by inducing mRNA expression and the activity of enzymes involved in detoxification of carcinogens and antioxidative defence.

  11. Cobalt and antimony: genotoxicity and carcinogenicity.

    Science.gov (United States)

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  12. Human exposure to trace elements through the skin by direct contact with clothing: Risk assessment

    Energy Technology Data Exchange (ETDEWEB)

    Rovira, Joaquim [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Catalonia (Spain); Nadal, Martí [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Schuhmacher, Marta [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Catalonia (Spain); Domingo, José L., E-mail: joseluis.domingo@urv.cat [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain)

    2015-07-15

    Metals in textile products and clothing are used for many purposes, such as metal complex dyes, pigments, mordant, catalyst in synthetic fabrics manufacture, synergists of flame retardants, antimicrobials, or as water repellents and odour-preventive agents. When present in textile materials, heavy metals may mean a potential danger to human health. In the present study, the concentrations of a number of elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Tl, V, and Zn) were determined in skin-contact clothes. Analysed clothes were made of different materials, colours, and brands. Interestingly, we found high levels of Cr in polyamide dark clothes (605 mg/kg), high Sb concentrations in polyester clothes (141 mg/kg), and great Cu levels in some green cotton fabrics (around 280 mg/kg). Dermal contact exposure and human health risks for adult males, adult females, and for <1-year-old children were assessed. Non-carcinogenic and carcinogenic risks were below safe (HQ<1) and acceptable (<10{sup −6}) limits, respectively, according to international standards. However, for Sb, non-carcinogenic risk was above 10% of the safety limit (HQ>0.1) for dermal contact with clothes. - Highlights: • We determined in skin-contact clothes the concentrations of a number of metals. • Dermal contact exposure and health risks for adults and for 1-year-old children were assessed. • Carcinogenic risks were considered as acceptable (<10{sup −6}). • For non-carcinogenic risks, only Sb exceeded a 10% of the HQ for dermal contact with clothes.

  13. Carcinogenicity of hair dye components.

    Science.gov (United States)

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer.

  14. Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

    Directory of Open Access Journals (Sweden)

    Jan Willem Van Der Laan

    2016-10-01

    Full Text Available In an exercise designed to reduce animal use, we analysed the results of rat sub-chronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumour outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred and forty-three of the 239 compounds not inducing putative preneoplastic lesions in the sub-chronic study did not induce tumours in the carcinogenicity study (True Negatives - TN, whereas 96 compounds were categorised as False Negatives (FN, because tumours were observed in the carcinogenicity study. For the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumours in the carcinogenicity study (True positives - TP, and 19 only showed preneoplastic lesions in subchronic studies but no tumours in the carcinogenicity study (False positives - FP. In addition, we then re-assessed the prediction of the tumour outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN. For 67 compounds the presence of cellular hyperplasia as evidence for proliferative action could be found (TP. Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92 % and the ability to detect carcinogens at 98 %. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorised as FN. 1 as FP, thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological

  15. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-07-15

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

  16. Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile.

    Science.gov (United States)

    Léonard, A; Gerber, G B; Stecca, C; Rueff, J; Borba, H; Farmer, P B; Sram, R J; Czeizel, A E; Kalina, I

    1999-05-01

    Acrylonitrile (AN) is an important intermediary for the synthesis of a variety of organic products, such as artificial fibres, household articles and resins. Although acute effects are the primary concern for an exposure to AN, potential genotoxic, carcinogenic and teratogenic risks of AN have to be taken seriously in view of the large number of workers employed in such industries and the world-wide population using products containing and possibly liberating AN. An understanding of the effect of acrylonitrile must be based on a characterization of its metabolism as well as of the resulting products and their genotoxic properties. Tests for mutagenicity in bacteria have in general been positive, those in plants and on unscheduled DNA synthesis doubtful, and those on chromosome aberrations in vivo negative. Wherever positive results had been obtained, metabolic activation of AN appeared to be a prerequisite. The extent to which such mutagenic effects are significant in man depends, however, also on the conditions of exposure. It appears from the limited data that the ultimate mutagenic factor(s), such as 2-cyanoethylene oxide, may have little opportunity to act under conditions where people are exposed because it is formed only in small amounts and is rapidly degraded. The carcinogenic action of AN has been evaluated by various agencies and ranged from 'reasonably be anticipated to be a human carcinogen' to 'cannot be excluded', the most recent evaluation being 'possibly carcinogenic to humans'. Animal data that confirm the carcinogenic potential of AN have certain limitations with respect to the choice of species, type of tumors and length of follow up. Epidemiological studies which sometimes, but not always, yielded positive results, encounter the usual difficulties of confounding factors in chemical industries. Exposure of workers to AN should continue to be carefully monitored, but AN would not have to be considered a cancer risk to the population provided

  17. [EVALUATION OF THE AIR POLLUTION HEALTH RISK FOR THE POPULATION OF THE CITY OF UFA].

    Science.gov (United States)

    Chuenkova, G A; Karelin, A O; Askarov, R A; Askarova, Z F

    2015-01-01

    There are presented results of the calculation of carcinogenic and non-carcinogenic risks due to the impact of chemical air pollutants for the human health of a large industrial city. Maximal levels of carcinogenic hazards under inhalation route of substances from the air were established to be noted on gasoline, manganese, sulfur dioxide, copper oxide, formaldehyde. In the formation of carcinogenic risk the greatest contribution is made by chromium, gasoline, formaldehyde, benzol. The risk of non-carcinogenic and carcinogenic effects for the population of the city continues to remain to be high, that requires the development and implementation of planned recreational measures.

  18. Transmission risk of human trichinellosis.

    Science.gov (United States)

    Takumi, Katsuhisa; Teunis, Peter; Fonville, Manoj; Vallee, Isabelle; Boireau, Pascal; Nöckler, Karsten; van der Giessen, Joke

    2009-02-23

    Trichinella is a food-borne parasitic zoonoses and human cases are still reported in Europe mainly due to the consumption of pig meat originating from small backyard farms. Infections originating from industrialized pig farming have not been reported for decades in Europe, due to control measures to prevent the transmission of Trichinella from wildlife by indoor housing and good management practices. Therefore, risk-based monitoring programs might replace individual carcass control in industrialized pig farming as described in EU legislation SANCO 2075/2005. Transmission of Trichinella species between wildlife and the risk that may pose to humans via consumption of contaminated pork meat has not been studied quantitatively. One pathway by which human trichinellosis can occur is the rat-pig-human route. To evaluate the transmission risk though this pathway the dose responses of rat, pig, and human were studied. Experimental T. spiralis infection was performed in rats with doses of as few as 10 parasites and the data set was analysed using a newly developed dose response model that describes larvae per gram (LPG). Experimental T. spiralis infection in pig was analysed in a similar way. Furthermore nine published outbreaks of human trichinellosis were analysed to determine the dose response in humans. The risk of human trichinellosis via the rat-pig-human transmission was simulated by the Monte Carlo method. A pair of female and male parasites representing the lowest infection pressure from the environment, led to the probability of human trichinellosis by consumption of 100g of raw pork meat equal to 5% via the studied rat-pig-human pathway. In the absence of rodent control near the farm, a low infection pressure from wildlife presents a relatively high risk of human trichinellosis via consumption of uncooked pork meat.

  19. Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.; McQuistan, Tammie J.; Henderson, Marilyn C.; Baird, William M.; Bench, Graham; Turteltaub, Ken W.; Williams, David E.

    2016-10-17

    Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

  20. Deoxyribonucleic acid repair gene X-ray repair cross-complementing group 1 polymorphisms and non-carcinogenic disease risk in different populations: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Bagher Larijani

    2013-01-01

    Full Text Available Purpose: This study aims to assess a meta-analysis of the association of X-ray repair cross-complementing group 1 (XRCC1 polymorphisms with the risk of various non-carcinogenic diseases in different population. Materials and Methods: This meta-analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian. Results: Pooled results showed no correlation between Arg194Trp and non-carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86-1.44 model in Asian population and dominant (OR = 1.04, 95% CI: 0.66-1.63 model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86-1.35 model of Asian population and quite well-correlation with recessive (OR = 1.49, 95% CI: 1.19-1.88, dominant (OR = 1.23, 95% CI: 0.94-1.62, and additive (OR = 1.23, 95% CI: 0.94-1.62 models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74-1.51. Conclusion: The present meta-analysis correspondingly shows that Arg399Gln variant to be associated with increased non-carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non-carcinogenic diseases.

  1. Friend or foe? The current epidemiologic evidence on selenium and human cancer risk.

    Science.gov (United States)

    Vinceti, Marco; Crespi, Catherine M; Malagoli, Carlotta; Del Giovane, Cinzia; Krogh, Vittorio

    2013-01-01

    Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders.

  2. Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans.

    Science.gov (United States)

    Walters, David G; Young, Philip J; Agus, Cynthia; Knize, Mark G; Boobis, Alan R; Gooderham, Nigel J; Lake, Brian G

    2004-09-01

    Consumption of red meat is associated with an increased risk of colorectal cancer, whereas cruciferous vegetable consumption reduces cancer risk. While the mechanisms remain to be determined, cruciferous vegetables may act by altering the metabolism of carcinogens present in cooked food, such as the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The aim of this study was to evaluate the effect of cruciferous vegetable consumption on the metabolism of PhIP in 20 non-smoking Caucasian male subjects. The study consisted of three 12-day phases, namely two periods of avoidance of cruciferous vegetables (phases 1 and 3) and a high cruciferous vegetable diet period (phase 2), when subjects ingested 250 g each of Brussels sprouts and broccoli per day. At the end of each study phase, the subjects consumed a cooked meat meal containing 4.90 microg PhIP and urine samples were collected for up to 48 h. Cruciferous vegetable consumption significantly increased hepatic CYP1A2, as demonstrated by changes in saliva caffeine kinetics. Samples of N(2)-hydroxy-PhIP-N(2)-glucuronide (the major urinary metabolite of PhIP in humans), N(2)-hydroxy-PhIP-N(3)-glucuronide and their trideuterated derivatives (to serve as internal standards) were synthesized and a liquid chromatography-mass spectrometry-mass spectrometry method developed for their analysis. In phases 1 and 3, the excretion of N(2)-hydroxy-N(2)-PhIP-glucuronide in 0-48 h urine samples was six times that of N(2)-hydroxy-PhIP-N(3)-glucuronide. Cruciferous vegetable consumption significantly increased the urinary excretion of N(2)-hydroxy-PhIP-N(2)-glucuronide in 0-48 h urine samples to 127 and 136% of levels observed in phases 1 and 3, respectively. In contrast, the urinary excretion of N(2)-hydroxy-PhIP-N(3)-glucuronide was unchanged. While the urinary excretion of both PhIP metabolites accounted for approximately 39% of the PhIP dose in phases 1 and 3, they accounted for approximately 49% of the

  3. Polymorphisms in genes related to activation or detoxification of carcinogens might interact with smoking to increase renal cancer risk: Results from The Netherlands Cohort Study on diet and cancer

    NARCIS (Netherlands)

    Smits, K.M.; Schouten, L.J.; Dijk, B.A.C. van; Houwelingen, K. van; Hulsbergen-Kaa, C.A. van de; Kiemeney, L.A.L.M.; Houwelingen, K. van; Goldbohm, R.A.; Oosterwijk, E.; Brandt, P.A. van den

    2008-01-01

    Metabolic gene polymorphisms have previously been suggested as risk factors for renal cell carcinoma (RCC). These polymorphisms are involved in activation or detoxification of carcinogens in cigarette smoke which is another RCC risk factor. We evaluated gene-environment interactions between CYP1A1,

  4. Is dermatologic usage of coal tar carcinogenic? A review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Pion, I.A.; Koenig, K.L.; Lim, H.W. [New York VA Medical Center, New York, NY (United States)

    1995-03-01

    Coal tar ointments have been used for decades in the treatment of various dermatoses, most notably eczema and psoriasis. Occupational exposure to coal tar poses an increased risk of developing cutaneous malignancies. The evidence of an increased risk of skin cancer in humans, as a result of dermatologic usage of tar, however, is conflicting. A consensus on the carcinogenicity of tar was sought. The existing literature (in vitro, animal and human studies) on this subject was reviewed. The carcinogenicity of coal tar was clearly demonstrated by in vitro and animal studies, and appears to be potentiated by concomitant use of ultraviolet radiation. Systemic absorption of mutagens from topically applied tar has been demonstrated in humans. Epidemiologic studies in humans, however, have not definitively shown an increase in skin cancer with therapeutic use of tar. Conclusive evidence for the carcinogenicity of tar used in dermatologic practice is lacking. Further controlled studies are necessary. 49 refs., 1 tab.

  5. Prenatal exposure of mice to the human liver carcinogen Aflatoxin B1 reveals a critical window of susceptibility to genetic change

    OpenAIRE

    2014-01-01

    It has become axiomatic that critical windows of susceptibility to genotoxins exist and that genetic damage in utero may be a trigger for later life cancers. Data supporting this critical window hypothesis are remarkably few. This study provides a quantitative bridge between DNA damage by the liver carcinogen aflatoxin B1 (AFB1) during prenatal development and the risk of later life genetic disease. AFB1 was given to pregnant C57BL/6J mice, carrying F1 gestation day 14 (GD14) embryos of the B...

  6. Mapping of HPV transcripts in four human cervical lesions using RNAseq suggests quantitative rearrangements during carcinogenic progression.

    Science.gov (United States)

    Chen, Jinmiao; Xue, Yuezhen; Poidinger, Michael; Lim, Thimothy; Chew, Sung Hock; Pang, Chai Ling; Abastado, Jean-Pierre; Thierry, Françoise

    2014-08-01

    Two classes of Human papillomaviruses (HPV) infect the anogenital track: high risk viruses that are associated with risk of cervical cancer and low risk types that drive development of benign lesions, such as condylomas. In the present study, we established quantitative transcriptional maps of the viral genome in clinical lesions associated with high risk HPV16 or low risk HPV6b. Marked qualitative and quantitative changes in the HPV16 transcriptome were associated with progression from low to high grade lesions. Specific transcripts encoding essential regulatory proteins such as E7, E2, E1^E4 and E5 were identified. We also identified intrinsic differences between the HPV6b-associated condyloma transcript map and that of the HPV16-associated low grade CIN specifically regarding promoter usage. Characterization and quantification of HPV transcripts in patient samples thus establish the impact of viral transcriptional regulation on the status of HPV-associated lesions and may therefore help in defining new biologically-relevant prognosis markers. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    Science.gov (United States)

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

  8. Potential ecological and human health risks of heavy metals in surface soils associated with iron ore mining in Pahang, Malaysia.

    Science.gov (United States)

    Diami, Siti Merryan; Kusin, Faradiella Mohd; Madzin, Zafira

    2016-10-01

    The composition of heavy metals (and metalloid) in surface soils of iron ore mine-impacted areas has been evaluated of their potential ecological and human health risks. The mining areas included seven selected locations in the vicinity of active and abandoned iron ore-mining sites in Pahang, Malaysia. Heavy metals such as Fe, Mn, Cu, Zn, Co, Pb, Cr, Ni, and Cd and metalloid As were present in the mining soils of the studied area, while Cu was found exceeding the soil guideline value at all sampling locations. However, the assessment of the potential ecological risk index (RI) indicated low ecological risk (RI between 44 and 128) with respect to Cd, Pb, Cu, As, Zn, Co, and Ni in the surface soils. Contributions of potential ecological risk [Formula: see text]by metal elements to the total potential ecological RI were evident for Cd, As, Pb, and Cu. Contribution of Cu appears to be consistently greater in the abandoned mining area compared to active iron ore-mining site. For non-carcinogenic risk, no significant potential health risk was found to both children and adults as the hazard indices (HIs) were all below than 1. The lifetime cancer risk (LCR) indicated that As has greater potential carcinogenic risk compared to other metals that may induce carcinogenic effects such as Pb, Cr, and Cd, while the LCR of As for children fell within tolerable range for regulatory purposes. Irrespective of carcinogenic or non-carcinogenic risk, greater potential health risk was found among children (by an order of magnitude higher for most metals) compared to adults. The hazard quotient (HQ) and cancer risk indicated that the pathways for the risk to occur were found to be in the order of ingestion > dermal > inhalation. Overall, findings showed that some metals and metalloid were still present at comparable concentrations even long after cessation of the iron ore-mining activities.

  9. Dose-response relationships for carcinogens: a review.

    OpenAIRE

    Zeise, L; Wilson, R.; Crouch, E A

    1987-01-01

    We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinea...

  10. DNA Adduct Formation from Metabolic 5'-Hydroxylation of the Tobacco-Specific Carcinogen N'-Nitrosonornicotine in Human Enzyme Systems and in Rats.

    Science.gov (United States)

    Zarth, Adam T; Upadhyaya, Pramod; Yang, Jing; Hecht, Stephen S

    2016-03-21

    N'-Nitrosonornicotine (NNN) is carcinogenic in multiple animal models and has been evaluated as a human carcinogen. NNN can be metabolized by cytochrome P450s through two activation pathways: 2'-hydroxylation and 5'-hydroxylation. While most previous studies have focused on 2'-hydroxylation in target tissues of rats, available evidence suggests that 5'-hydroxylation is a major activation pathway in human enzyme systems, in nonhuman primates, and in target tissues of some other rodent carcinogenicity models. In the study reported here, we investigated DNA damage resulting from NNN 5'-hydroxylation by quantifying the adduct 2-(2-(3-pyridyl)-N-pyrrolidinyl)-2'-deoxyinosine (py-py-dI). In rats treated with NNN in the drinking water (7-500 ppm), py-py-dI was the major DNA adduct resulting from 5'-hydroxylation of NNN in vivo. Levels of py-py-dI in the lung and nasal cavity were the highest, consistent with the tissue distribution of CYP2A3. In rats treated with (S)-NNN or (R)-NNN, the ratios of formation of (R)-py-py-dI to (S)-py-py-dI were not the expected mirror image, suggesting that there may be a carrier for one of the unstable intermediates formed upon 5'-hydroxylation of NNN. Rat hepatocytes treated with (S)- or (R)-NNN or (2'S)- or (2'R)-5'-acetoxyNNN exhibited a pattern of adduct formation similar to that of live rats. In vitro studies with human liver S9 fraction or human hepatocytes incubated with NNN (2-500 μM) demonstrated that py-py-dI formation was greater than the formation of pyridyloxobutyl-DNA adducts resulting from 2'-hydroxylation of NNN. (S)-NNN formed more total py-py-dI adducts than (R)-NNN in human liver enzyme systems, which is consistent with the critical role of CYP2A6 in the 5'-hydroxylation of NNN in human liver. The results of this study demonstrate that the major DNA adduct resulting from NNN metabolism by human enzymes is py-py-dI and provide potentially important new insights into the metabolic activation of NNN in rodents and humans.

  11. trans-11 18:1 Vaccenic Acid (TVA Has a Direct Anti-Carcinogenic Effect on MCF-7 Human Mammary Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ji-Na Lim

    2014-02-01

    Full Text Available Trans vaccenic acid (TVA; trans-11 18:1 is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA, a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1 in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products.

  12. Assessment of the DNA Damage in Human Sperm and Lymphocytes Exposed to the Carcinogen Food Contaminant Furan with Comet Assay

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2015-10-01

    Full Text Available ABSTRACTThe aim of this work was to assess the damage of DNA in human blood cell and spermin vitro under the influence of furan. These cells were administered 0-600 μM of furan at 37 and 32oC for 30 and 60 min, respectively. A significant increase in tail DNA%, tail length and moment indicating DNA damage was observed at increasing doses when compared to the controls. The treatment with 300 and 600 μM of furan showed a maximum increase of 86.74 ± 2.43 and 93.29 ± 8.68 compared to the control tail DNA% in lymphocytes. However, only 600 μM of furan showed a maximum increase of 94.71 ± 6.24 compared to the control tail DNA% in sperm. The results suggested that furan caused DNA damage in lymphocytes at increasing doses, but appeared to have not the same effect on human sperm at the low doses. Genotoxic activity had an impact on the risk assessment of furan formed on the food for human cells. Therefore, it would be important to further investigate these properties of furan as the food mutagen.

  13. Human Health Risk Assessment and Safety Threshold of Harmful Trace Elements in the Soil Environment of the Wulantuga Open-Cast Coal Mine

    Directory of Open Access Journals (Sweden)

    Jianli Jia

    2015-11-01

    Full Text Available In this study, soil samples were collected from a large-scale open-cast coal mine area in Inner Mongolia, China. Arsenic (As, cadmium (Cd, beryllium (Be and nickel (Ni in soil samples were detected using novel collision/reaction cell technology (CCT with inductively-coupled plasma mass spectrometry (ICP-MS; collectively ICP-CCT-MS after closed-vessel microwave digestion. Human health risk from As, Cd, Be and Ni was assessed via three exposure pathways—inhalation, skin contact and soil particle ingestion. The comprehensive carcinogenic risk from As in Wulantuga open-cast coal mine soil is 6.29–87.70-times the acceptable risk, and the highest total hazard quotient of As in soils in this area can reach 4.53-times acceptable risk levels. The carcinogenic risk and hazard quotient of Cd, Be and Ni are acceptable. The main exposure route of As from open-cast coal mine soils is soil particle ingestion, accounting for 76.64% of the total carcinogenic risk. Considering different control values for each exposure pathway, the minimum control value (1.59 mg/kg could be selected as the strict reference safety threshold for As in the soil environment of coal-chemical industry areas. However, acceptable levels of carcinogenic risk are not unanimous; thus, the safety threshold identified here, calculated under a 1.00 × 10−6 acceptable carcinogenic risk level, needs further consideration.

  14. Nitrate and nitrite in the diet: how to assess their benefit and risk for human health.

    Science.gov (United States)

    Habermeyer, Michael; Roth, Angelika; Guth, Sabine; Diel, Patrick; Engel, Karl-Heinz; Epe, Bernd; Fürst, Peter; Heinz, Volker; Humpf, Hans-Ulrich; Joost, Hans-Georg; Knorr, Dietrich; de Kok, Theo; Kulling, Sabine; Lampen, Alfonso; Marko, Doris; Rechkemmer, Gerhard; Rietjens, Ivonne; Stadler, Richard H; Vieths, Stefan; Vogel, Rudi; Steinberg, Pablo; Eisenbrand, Gerhard

    2015-01-01

    Nitrate is a natural constituent of the human diet and an approved food additive. It can be partially converted to nitrogen monoxide, which induces vasodilation and thereby decreases blood pressure. This effect is associated with a reduced risk regarding cardiovascular disease, myocardial infarction, and stroke. Moreover, dietary nitrate has been associated with beneficial effects in patients with gastric ulcer, renal failure, or metabolic syndrome. Recent studies indicate that such beneficial health effects due to dietary nitrate may be achievable at intake levels resulting from the daily consumption of nitrate-rich vegetables. N-nitroso compounds are endogenously formed in humans. However, their relevance for human health has not been adequately explored up to now. Nitrate and nitrite are per se not carcinogenic, but under conditions that result in endogenous nitrosation, it cannot be excluded that ingested nitrate and nitrite may lead to an increased cancer risk and may probably be carcinogenic to humans. In this review, the known beneficial and detrimental health effects related to dietary nitrate/nitrite intake are described and the identified gaps in knowledge as well as the research needs required to perform a reliable benefit/risk assessment in terms of long-term human health consequences due to dietary nitrate/nitrite intake are presented.

  15. Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-05-11

    A relatively simple, quantitative approach is proposed to address a specific, important gap in the appr approach recommended by the USEPA Guidelines for Cancer Risk Assessment to oach address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate 'linear' (genotoxic) vs. 'nonlinear' (nongenotoxic) approaches to low low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient t to parameterize a biologically based model that reliably o extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach - similar to that used in reference dose procedures for classic toxicity endpoints - can address MOA uncertainty in a way that avoids explicit modeling of low low-dose risk as a function of administere administered or internal dose. Even when a 'nonlinear' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was i illustrated llustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based p

  16. International Conference on Harmonisation; proposed change to rodent carcinogenicity testing of pharmaceuticals; request for comments. Notice; request for comments.

    Science.gov (United States)

    2013-03-18

    The Food and Drug Administration (FDA or the Agency) is considering a proposed change to the International Conference on Harmonisation (ICH) Sl guidance on rodent carcinogenicity testing. The goal of this potential change is to introduce a more comprehensive and integrated approach to address the risk of human carcinogenicity of small molecule pharmaceuticals, and to define conditions under which 2-year rodent carcinogenicity studies add value to that assessment. The basis of this proposed change is the retrospective analyses of several datasets that reflect three decades of experience with such studies. The datasets suggest that knowledge of certain pharmacologic and toxicologic data can sometimes provide sufficient information to anticipate the outcome of 2-year rodent studies and their potential value in predicting the risk of human carcinogenicity of a given pharmaceutical. FDA is requesting public comment regarding a proposed change in approach to carcinogenicity assessment, on the prospective evaluation period intended to test this new approach, and on the proposed weight-of-evidence factors for carcinogenicity assessment.

  17. Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-01-30

    As reflected in the 2005 USEPA Guidelines for Cancer Risk Assessment, some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate ''linear'' (genotoxic) vs. ''nonlinear'' (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach--similar to that used in reference dose procedures for classic toxicity endpoints--can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a ''nonlinear'' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for the rodent carcinogen naphthalene. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Resulting

  18. [THE COMPARATIVE ANALYSIS OF RESULTS OF DETECTION OF CARCINOGENIC TYPES OF HUMAN PAPILLOMA VIRUS BY QUALITATIVE AND QUANTITATIVE TESTS].

    Science.gov (United States)

    Kuzmenko, E T; Labigina, A V; Leshenko, O Ya; Rusanov, D N; Kuzmenko, V V; Fedko, L P; Pak, I P

    2015-05-01

    The analysis of results of screening (n = 3208; sexually active citizen aged from 18 to 59 years) was carried out to detect oncogene types of human papilloma virus in using qualitative (1150 females and 720 males) and quantitative (polymerase chain reaction in real-time (843 females and 115 males) techniques. The human papilloma virus of high oncogene type was detected in 65% and 68.4% of females and in 48.6% and 53% of males correspondingly. Among 12 types of human papilloma virus the most frequently diagnosed was human papilloma virus 16 independently of gender of examined and technique of analysis. In females, under application of qualitative tests rate of human papilloma virus 16 made up to 18.3% (n = 280) and under application of quantitative tests Rte of human papilloma virus made up to 14.9% (n = 126; p ≤ 0.05). Under examination of males using qualitative tests rate of human papilloma virus 16 made up to 8.3% (n = 60) and under application of qualitative tests made up to 12.2% (n = 14; p ≥ 0.05). Under application of qualitative tests rate of detection on the rest ofoncogene types of human papilloma virus varied in females from 3.4% to 8.4% and in males from 1.8% to 5.9%. Under application of qualitative tests to females rate of human papilloma virus with high viral load made up to 68.4%, with medium viral load - 2.85% (n = 24) and with low viral load -0.24% (n = 2). Under application of quantitative tests in males rate of detection of types of human papilloma virus made up to 53% and at that in all high viral load was established. In females, the most of oncogene types of human papilloma virus (except for 31, 39, 59) are detected significantly more often than in males.

  19. Assessing Human Health Risk from Pesticides

    Science.gov (United States)

    EPA protects human health and the environment by evaluating the risk associated with pesticides before allowing them to be used in the United States. Learn about the tools and processes used in risk assessment for pesticides.

  20. NASA Human System Risk Assessment Process

    Science.gov (United States)

    Francisco, D.; Romero, E.

    2016-01-01

    NASA utilizes an evidence based system to perform risk assessments for the human system for spaceflight missions. The center of this process is the multi-disciplinary Human System Risk Board (HSRB). The HSRB is chartered from the Chief Health and Medical Officer (OCHMO) at NASA Headquarters. The HSRB reviews all human system risks via an established comprehensive risk and configuration management plan based on a project management approach. The HSRB facilitates the integration of human research (terrestrial and spaceflight), medical operations, occupational surveillance, systems engineering and many other disciplines in a comprehensive review of human system risks. The HSRB considers all factors that influence human risk. These factors include pre-mission considerations such as screening criteria, training, age, sex, and physiological condition. In mission factors such as available countermeasures, mission duration and location and post mission factors such as time to return to baseline (reconditioning), post mission health screening, and available treatments. All of the factors influence the total risk assessment for each human risk. The HSRB performed a comprehensive review of all potential inflight medical conditions and events and over the course of several reviews consolidated the number of human system risks to 30, where the greatest emphasis is placed for investing program dollars for risk mitigation. The HSRB considers all available evidence from human research and, medical operations and occupational surveillance in assessing the risks for appropriate mitigation and future work. All applicable DRMs (low earth orbit for 6 and 12 months, deep space for 30 days and 1 year, a lunar mission for 1 year, and a planetary mission for 3 years) are considered as human system risks are modified by the hazards associated with space flight such as microgravity, exposure to radiation, distance from the earth, isolation and a closed environment. Each risk has a summary

  1. Consumption of organic meat does not diminish the carcinogenic potential associated with the intake of persistent organic pollutants (POPs).

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valerón, Pilar F; Camacho, María; Zumbado, Manuel; Almeida-González, Maira; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2017-02-01

    Numerous studies have shown an epidemiological link between meat consumption and the incidence of cancer, and it has been suggested that this relationship may be motivated by the presence of carcinogenic contaminants on it. Among the most frequently detected contaminants in meat are several types of persistent organic pollutants (POPs), and it is well known that many of them are carcinogenic. On the other hand, an increasing number of consumers choose to feed on what are perceived as healthier foods. Thus, the number of consumers of organic food is growing. However, environmental contamination by POPs is ubiquitous, and it is therefore unlikely that the practices of organic food production are able to prevent this contamination. To test this hypothesis, we acquired 76 samples of meat (beef, chicken, and lamb) of two modes of production (organic and conventional) and quantified their levels of 33 carcinogenic POPs. On this basis, we determined the human meat-related daily dietary exposure to these carcinogens using as a model a population with a high consumption of meat, such as the Spanish population. The maximum allowable meat consumption for this population and the carcinogenic risk quotients associated with the current pattern of consumption were calculated. As expected, no sample was completely free of carcinogenic contaminants, and the differences between organically and conventionally produced meats were minimal. According to these results, the current pattern of meat consumption exceeded the maximum limits, which are set according to the levels of contaminations, and this is associated with a relevant carcinogenic risk. Strikingly, the consumption of organically produced meat does not diminish this carcinogenic risk, but on the contrary, it seems to be even higher, especially that associated with lamb consumption.

  2. The carcinogenicity of the biocide ortho-phenylphenol.

    Science.gov (United States)

    Appel, K E

    2000-04-01

    The biocides ortho-phenylphenol and its sodium salt (OPP and SOPP) are widely used as fungicides and antibacterial agents for commercial and consumer purposes. The carcinogenicity of OPP/SOPP toward the urinary bladder was demonstrated when rats were chronically fed concentrations of 0.5%-4% in their diet. Other species tested so far did not develop tumours. Understanding the mechanisms underlying OPP/SOPP-induced bladder carcinogenesis is critical to determine whether risks observed at high doses in rats are of relevance to humans exposed at much lower levels. This overview details experimental studies of carcinogenicity, genotoxicity as well as metabolism/toxicokinetics and other mechanistic studies which bear on cancer hazard and risk evaluation of exposure to humans. Based on the presently available knowledge, it is concluded that reactive quinoid metabolites exhibiting redox cycling activities are the crucial factors. At certain concentration levels, these metabolites are able to produce cytotoxic events with concomitant enhanced cell proliferation of the target tissue. Further important risk factors are probably promutagenic lesions induced by oxidative stress and a higher urinary pH. Supposed that these mechanisms are the basis for the tumourigenicity observed, then suitable low doses of OPP/SOPP will practically pose no cancer risk.

  3. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Bonassi, S; Hagmar, L; Strömberg, U

    2000-01-01

    An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role p...

  4. The ISS Carcinogens Data Bank (BDC).

    Science.gov (United States)

    Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Marcello, Ida

    2008-01-01

    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents.

  5. Evaluation of the carcinogenic potential of pharmaceuticals. Opportunities arising from the International Conference on Harmonisation.

    Science.gov (United States)

    Monro, A M; MacDonald, J S

    1998-05-01

    The evaluation of the carcinogenic potential of pharmaceuticals is currently undergoing dramatic changes. For the past 25 years the regulatory expectation for agents intended for long term use has been that lifespan studies (usually lasting 2 years) in 2 rodent species be conducted. These studies take at least 3 years to plan, execute and interpret, and use over 1200 animals. It is now recognised that the quality of the information obtained from these studies is unreliable for prediction of carcinogenic risk to humans. Over the past 4 years, the International Conference on Harmonisation (ICH) has recommended changes in approaches to assessing the carcinogenic potential of pharmaceuticals. In future, only one long term rodent study will be routinely required (usually in rats), provided this is complemented with a short or medium term test in one of the emerging new models for carcinogenicity, such as transgenic mice or newborn mice. However, the relevance of these new models to human cancer and their use in risk assessment is still largely unknown and this situation must be kept under review as knowledge accumulates. A long term study in a second rodent species is still an option. Dose selection has also been improved inasmuch as there are now several alternatives to the use of the maximum tolerated dose (MTD). In the past, the use of the MTD, when the normal homeostasis of the test animals is disturbed, has been considered one of the major problems with the rodent carcinogenicity bioassay. However, one of the alternative end-points to the use of the MTD, i.e. the comparison of plasma concentrations in rodents and humans, must be viewed with caution. While this may contribute to limiting the high dose level for agents of very low toxicity, the concept should not be interpreted as signifying that plasma concentrations provide a sound basis for comparing the carcinogenic activity of agents in different species. Recognition of the 4 properties (genotoxicity

  6. An Overview of Carcinogenic Heavy Metal: Molecular Toxicity Mechanism and Prevention

    Science.gov (United States)

    Kim, Hyun Soo; Kim, Yeo Jin; Seo, Young Rok

    2015-01-01

    Almost all heavy metals are serious toxicants as carcinogens. However, due to their chemical and physiological properties, heavy metals are useful in industrial areas including alloy, smelting and production of commercial products. Such applications increase the opportunity for heavy metal exposure. Waste from industrial processes is also a major source of environmental contamination and accumulation in the human body. Arsenic, cadmium, chromium, and nickel are classified as group 1 carcinogens by the International Agency for Research on Cancer, and are utilized commercially. In this review, we used molecular pathway analysis to understand the toxicity and carcinogenic mechanisms of these metals. Our analyzed data showed that above-mentioned metallic substances induce oxidative stress, DNA damage, and cell death processes, resulting in increase the risk of cancer and cancer-related diseases. Thus, we might think phytochelatin molecules and antioxidative phytochemical substances are helpful for prevention of heavy metal-induced cancer. PMID:26734585

  7. Carcinogen-Induced Hepatic Tumors in KLF6+/- Mice Recapitulate Aggressive Human Hepatocellular Carcinoma Associated with p53 Pathway Deregulation

    NARCIS (Netherlands)

    Tarocchi, Mirko; Hannivoort, Rebekka; Hoshida, Yujin; Lee, Ursula E.; Vetter, Diana; Narla, Goutham; Villanueva, Augusto; Oren, Moshe; Llovet, Josep M.; Friedman, Scott L.

    2011-01-01

    Inactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental hepatocarcinoge

  8. Polycyclic Aromatic Hydrocarbons (PAHs) and their Bioaccessibility in Meat: a Tool for Assessing Human Cancer Risk.

    Science.gov (United States)

    Hamidi, Elliyana Nadia; Hajeb, Parvaneh; Selamat, Jinap; Abdull Razis, Ahmad Faizal

    2016-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are primarily formed as a result of thermal treatment of food, especially barbecuing or grilling. Contamination by PAHs is due to generation by direct pyrolysis of food nutrients and deposition from smoke produced through incomplete combustion of thermal agents. PAHs are ubiquitous compounds, well-known to be carcinogenic, which can reach the food in different ways. As an important human exposure pathway of contaminants, dietary intake of PAHs is of increasing concern for assessing cancer risk in the human body. In addition, the risks associated with consumption of barbecued meat may increase if consumers use cooking practices that enhance the concentrations of contaminants and their bioaccessibility. Since total PAHs always overestimate the actual amount that is available for absorption by the body, bioaccessibility of PAHs is to be preferred. Bioaccessibility of PAHs in food is the fraction of PAHs mobilized from food matrices during gastrointestinal digestion. An in vitro human digestion model was chosen for assessing the bioaccessibility of PAHs in food as it offers a simple, rapid, low cost alternative to human and animal studies; providing insights which may not be achievable in in vivo studies. Thus, this review aimed not only to provide an overview of general aspects of PAHs such as the formation, carcinogenicity, sources, occurrence, and factors affecting PAH concentrations, but also to enhance understanding of bioaccessibility assessment using an in vitro digestion model.

  9. Potent inhibition of human 5-lipoxygenase and microsomal prostaglandin E₂ synthase-1 by the anti-carcinogenic and anti-inflammatory agent embelin.

    Science.gov (United States)

    Schaible, Anja M; Traber, Heidi; Temml, Veronika; Noha, Stefan M; Filosa, Rosanna; Peduto, Antonella; Weinigel, Christina; Barz, Dagmar; Schuster, Daniela; Werz, Oliver

    2013-08-15

    Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) possesses anti-inflammatory and anti-carcinogenic properties in vivo, and these features have been related to interference with multiple targets including XIAPs, NFκB, STAT-3, Akt and mTOR. However, interference with these proteins requires relatively high concentrations of embelin (IC₅₀>4 μM) and cannot fully explain its bioactivity observed in several functional studies. Here we reveal human 5-lipoxygenase (5-LO) and microsomal prostaglandin E₂ synthase (mPGES)-1 as direct molecular targets of embelin. Thus, embelin potently suppressed the biosynthesis of eicosanoids by selective inhibition of 5-LO and mPGES-1 with IC₅₀=0.06 and 0.2 μM, respectively. In intact human polymorphonuclear leukocytes and monocytes, embelin consistently blocked the biosynthesis of various 5-LO products regardless of the stimulus (fMLP or A23187) with IC₅₀=0.8-2 μM. Neither the related human 12- and 15-LO nor the cyclooxygenases-1 and -2 or cytosolic phospholipase A₂ were significantly affected by 10 μM embelin. Inhibition of 5-LO and mPGES-1 by embelin was (I) essentially reversible after wash-out, (II) not impaired at higher substrate concentrations, (III) unaffected by inclusion of Triton X-100, and (IV) did not correlate to its proposed antioxidant properties. Docking simulations suggest concrete binding poses in the active sites of both 5-LO and mPGES-1. Because 5-LO- and mPGES-1-derived eicosanoids play roles in inflammation and cancer, the interference of embelin with these enzymes may contribute to its biological effects and suggests embelin as novel chemotype for development of dual 5-LO/mPGES-1 inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Short-term exposure of nontumorigenic human bronchial epithelial cells to carcinogenic chromium(VI) compromises their respiratory capacity and alters their bioenergetic signature.

    Science.gov (United States)

    Cerveira, Joana F; Sánchez-Aragó, María; Urbano, Ana M; Cuezva, José M

    2014-01-01

    Previous studies on the impact of hexavalent chromium [Cr(VI)] on mammalian cell energetics revealed alterations suggestive of a shift to a more fermentative metabolism. Aiming at a more defined understanding of the metabolic effects of Cr(VI) and of their molecular basis, we assessed the impact of a mild Cr(VI) exposure on critical bioenergetic parameters (lactate production, oxygen consumption and intracellular ATP levels). Cells derived from normal human bronchial epithelium (BEAS-2B cell line), the main in vivo target of Cr(VI) carcinogenicity, were subjected for 48 h to 1 μM Cr(VI). We could confirm a shift to a more fermentative metabolism, resulting from the simultaneous inhibition of respiration and stimulation of glycolysis. This shift was accompanied by a decrease in the protein levels of the catalytic subunit (subunit β) of the mitochondrial H(+)-ATP synthase (β-F1-ATPase) and a concomitant marked increase in those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The corresponding alteration in the β-F1-ATPase/GAPDH protein ratio (viewed as a bioenergetic signature) upon Cr(VI) exposure was in agreement with the observed attenuation of cellular respiration and enhancement of glycolytic flux. Altogether, these results constitute a novel finding in terms of the molecular mechanisms of Cr(VI) effects.

  11. Short-term exposure of nontumorigenic human bronchial epithelial cells to carcinogenic chromium(VI compromises their respiratory capacity and alters their bioenergetic signature

    Directory of Open Access Journals (Sweden)

    Joana F. Cerveira

    2014-01-01

    Full Text Available Previous studies on the impact of hexavalent chromium [Cr(VI] on mammalian cell energetics revealed alterations suggestive of a shift to a more fermentative metabolism. Aiming at a more defined understanding of the metabolic effects of Cr(VI and of their molecular basis, we assessed the impact of a mild Cr(VI exposure on critical bioenergetic parameters (lactate production, oxygen consumption and intracellular ATP levels. Cells derived from normal human bronchial epithelium (BEAS-2B cell line, the main in vivo target of Cr(VI carcinogenicity, were subjected for 48 h to 1 μM Cr(VI. We could confirm a shift to a more fermentative metabolism, resulting from the simultaneous inhibition of respiration and stimulation of glycolysis. This shift was accompanied by a decrease in the protein levels of the catalytic subunit (subunit β of the mitochondrial H+-ATP synthase (β-F1-ATPase and a concomitant marked increase in those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH. The corresponding alteration in the β-F1-ATPase/GAPDH protein ratio (viewed as a bioenergetic signature upon Cr(VI exposure was in agreement with the observed attenuation of cellular respiration and enhancement of glycolytic flux. Altogether, these results constitute a novel finding in terms of the molecular mechanisms of Cr(VI effects.

  12. Ultraviolet Radiation: Human Exposure and Health Risks.

    Science.gov (United States)

    Tenkate, Thomas D.

    1998-01-01

    Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

  13. Beryllium: genotoxicity and carcinogenicity.

    Science.gov (United States)

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  14. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  15. Carcinogenic effects of benzene: Cesare Maltoni's contributions.

    Science.gov (United States)

    Mehlman, Myron A

    2002-12-01

    Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

  16. Tobacco carcinogens, their biomarkers and tobacco-induced cancer.

    Science.gov (United States)

    Hecht, Stephen S

    2003-10-01

    The devastating link between tobacco products and human cancers results from a powerful alliance of two factors - nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?

  17. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane.

    Science.gov (United States)

    Bauman, Julie E; Zang, Yan; Sen, Malabika; Li, Changyou; Wang, Lin; Egner, Patricia A; Fahey, Jed W; Normolle, Daniel P; Grandis, Jennifer R; Kensler, Thomas W; Johnson, Daniel E

    2016-07-01

    Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.

  18. Integrating Spaceflight Human System Risk Research

    Science.gov (United States)

    Mindock, Jennifer; Lumpkins, Sarah; Anton, Wilma; Havenhill, Maria; Shelhamer, Mark; Canga, Michael

    2016-01-01

    NASA is working to increase the likelihood of human health and performance success during exploration missions as well as to maintain the subsequent long-term health of the crew. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. "Human System Risks" (Risks) have been identified, and approximately 30 are being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

  19. Human Health and Ecological Risk Assessment for the Operation of the Explosives Waste Treatment Facility at Site 300 of the Lawrence Livermore National Laboratory, Volume 1: Report of Results

    Energy Technology Data Exchange (ETDEWEB)

    Gallegtos, G M; Daniels, J I; Wegrecki, A M

    2007-03-16

    Human health and ecological risk assessments are required as part of the Resource Recovery and Conservation Act (RCRA) permit renewal process for waste treatment units. This risk assessment is prepared in support of the RCRA permit renewal for the Explosives Waste Treatment Facility (EWTF) at Site 300 of the Lawrence Livermore National Laboratory (LLNL). The human health risk assessment is based on U.S. Environmental Protection Agency- (U.S. EPA) approved emissions factors and on California Environmental Protection Agency (CalEPA), California Air Resources Board (CARB) and U.S. EPA assessment and air dispersion models. This risk assessment identifies the receptors of concern and evaluates theoretical carcinogenic risk, and theoretical acute and chronic non-carcinogenic hazard, following those guidelines. The carcinogenic risk to a 30-year resident at the maximum off-site receptor location is 0.0000006 or 0.6 in 1 million. The carcinogenic risk to a 25-year worker at the maximum bystander on-site receptor location is also 0.0000006 or 0.6 in 1 million. Any risk of less than 1 in a million is below the level of regulatory concern. The acute non-carcinogenic hazard for the 30-year resident is 0.01, and the chronic non-carcinogenic hazard is 0.01. The acute non-carcinogenic hazard for the 25-year worker is 0.3, and the chronic non-carcinogenic hazard is 0.2. The point of comparison for acute and chronic non-carcinogenic hazard is 1.0; an estimate less than 1.0 is below the level of regulatory concern. The estimates of health effects are based on health conservative assumptions and represent an upper bound of the possible exposures to the receptors. Based on these results, emissions from the operations of the EWTF should not be of concern for human health. For the ecological risk assessment (ERA), 10 receptor species (including plants), representing members of the trophic levels in the habitat of Site 300, were evaluated for the possibility of potential detrimental

  20. Scientific analysis of the proposed uses of the T25 dose descriptor in chemical carcinogen regulation.

    Science.gov (United States)

    Roberts, R A; Crump, K S; Lutz, W K; Wiegand, H J; Williams, G M; Harrison, P T; Purchase, I F

    2001-11-01

    harmonisation of approaches to risk assessment for all genotoxic and nongenotoxic carcinogens. In summary, the T25 method has utility for ranking potency to focus efforts in risk reduction. However, uncertainties such as the false assumption of precision and non-linearity in the dose-response curve for tumour induction raise serious concerns that caution against the use of T25/linear method for predicting human cancer risk.

  1. Techniques for carcinogenicity studies.

    Science.gov (United States)

    Weisburger, E K

    1981-09-01

    Short-term tests to detect genetic, chromosomal, or DNA damage are now required by regulatory agencies for any new compound proposed for commercial production. Furthermore, full-scale carcinogenicity tests may be required for certain compounds. In this circumstance, the compound-related factors including stability, purity, physical properties, and chemical structure and reactivity must be considered. Animal factors include species and strain of test animal, route of administration, age, sex, diet, and spontaneous tumor incidence. A team of qualified investigators with experience in various disciplines is required to conduct the studies properly. Quality control measures and adherence to the code of good laboratory practice are also necessary during all phases of the study. The investment in a carcinogenicity study therefore becomes fairly substantial in terms of both time and money.

  2. In Silico Methods for Carcinogenicity Assessment.

    Science.gov (United States)

    Golbamaki, Azadi; Benfenati, Emilio

    2016-01-01

    Screening compounds for potential carcinogenicity is of major importance for prevention of environmentally induced cancers. A large sequence of alternative predictive models, ranging from short-term biological assays (e.g. mutagenicity tests) to theoretical models, have been attempted in this field. Theoretical approaches such as (Q)SAR are highly desirable for identifying carcinogens, since they actively promote the replacement, reduction, and refinement of animal tests. This chapter reports and describes some of the most noted (Q)SAR models based on the human expert knowledge and statistically approach, aiming at predicting the carcinogenicity of chemicals. Additionally, the performance of the selected models has been evaluated and the results are interpreted in details by applying these prediction models to some pharmaceutical molecules.

  3. Flavonoids targeting of IκB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Tahanian E

    2011-05-01

    Full Text Available Elizabeth Tahanian¹, Luis Arguello Sanchez¹, Tze Chieh Shiao², René Roy², Borhane Annabi¹¹Centre de Recherche BioMED, ²Centre de Recherche PharmaQAM, Département de chimie, Université du Québec à Montréal, QC, CanadaAbstract: Brain endothelial cells play an essential role as structural and functional components of the blood–brain barrier (BBB. Increased BBB breakdown and brain injury are associated with neuroinflammation and are thought to trigger mechanisms involving matrix metalloproteinase upregulation. Emerging evidence also indicates that cyclooxygenase (COX inhibition limits BBB disruption, but the mechanisms linking metalloproteinase to COX remain unknown. In this study, we sought to investigate the nuclear factor-kappa B (NF-κB signaling pathway, a common pathway in both the regulation of matrix metalloproteinase-9 (MMP-9 and COX-2 expression, and the inhibitory properties of several chemopreventive flavonoids. Human brain microvascular endothelial cells were treated with a combination of phorbol 12-myristate 13-acetate (PMA, a carcinogen documented to increase MMP-9 and COX-2 through NF-κB, and several naturally occurring flavonoids. Among the molecules tested, we found that fisetin, apigenin, and luteolin specifically and dose-dependently antagonized PMA-induced COX-2 and MMP-9 gene and protein expressions as assessed by qRT-PCR, immunoblotting, and zymography respectively. We further demonstrate that flavonoids impact on IκK-mediated phosphorylation activity as demonstrated by the inhibition of PMA-induced IκB phosphorylation levels. Our results suggest that BBB disruption during neuroinflammation could be pharmacologically reduced by a specific class of flavonoids acting as NF-κB signal transduction inhibitors.Keywords: blood–brain barrier, flavonoids, neuroinflammation, NF-κB signal transduction inhibitors

  4. Revised Human Health Risk Assessment on Chlorpyrifos

    Science.gov (United States)

    We have revised our human health risk assessment and drinking water exposure assessment for chlorpyrifos that supported our October 2015 proposal to revoke all food residue tolerances for chlorpyrifos. Learn about the revised analysis.

  5. Integrating spaceflight human system risk research

    Science.gov (United States)

    Mindock, Jennifer; Lumpkins, Sarah; Anton, Wilma; Havenhill, Maria; Shelhamer, Mark; Canga, Michael

    2017-10-01

    NASA is working to increase the likelihood of exploration mission success and to maintain crew health, both during exploration missions and long term after return to Earth. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. ;Human System Risks; (Risks) have been identified, and 32 are currently being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

  6. Human System Risk Management for Space Flight

    Science.gov (United States)

    Davis, Jeffrey

    2015-01-01

    This brief abstract reviews the development of the current day approach to human system risk management for space flight and the development of the critical components of this process over the past few years. The human system risk management process now provides a comprehensive assessment of each human system risk by design reference mission (DRM) and is evaluated not only for mission success but also for long-term health impacts for the astronauts. The discipline of bioastronautics is the study of the biological and medical effects of space flight on humans. In 1997, the Space Life Sciences Directorate (SLSD) initiated the Bioastronautics Roadmap (Roadmap) as the "Critical Path Roadmap", and in 1998 participation in the roadmap was expanded to include the National Space Biomedical Research Institute (NSBRI) and the external community. A total of 55 risks and 250 questions were identified and prioritized and in 2000, the Roadmap was base-lined and put under configuration control. The Roadmap took into account several major advisory committee reviews including the Institute of Medicine (IOM) "Safe Passage: Astronaut care for Exploration Missions", 2001. Subsequently, three collaborating organizations at NASA HQ (Chief Health and Medical Officer, Office of Space Flight and Office of Biological & Physical Research), published the Bioastronautics Strategy in 2003, that identified the human as a "critical subsystem of space flight" and noted that "tolerance limits and safe operating bands must be established" to enable human space flight. These offices also requested a review by the IOM of the Roadmap and that review was published in October 2005 as "A Risk Reduction Strategy for Human Exploration of Space: A Review of NASA's Bioastronautics Roadmap", that noted several strengths and weaknesses of the Roadmap and made several recommendations. In parallel with the development of the Roadmap, the Office of the Chief Health and Medical Officer (OCHMO) began a process in

  7. Assessing hazardous risks of human exposure to temple airborne polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Chiang, Kuo-Chih; Chio, Chia-Pin; Chiang, Yu-Hui; Liao, Chung-Min

    2009-07-30

    We proposed an integrated probabilistic risk assessment framework based on reported data to quantify human health risks of temple goers/workers to airborne polycyclic aromatic hydrocarbons (PAHs) from incense burning in typical Taiwanese temples. The framework probabilistically integrates exposure, human respiratory tract, and incremental lifetime cancer risk (ILCR) models to quantitatively estimate size-dependent PAHs exposure in human lung regions and cancer risks for temple goers (moderate and high exposures) and temple workers (extreme exposure). Our results show that the ILCRs are greater than the acceptable level of 10(-6) for extreme and high exposure groups through inhalation route. The result also indicates that the higher ILCRs (10(-6) to 10(-4)) are found in ingestion and dermal contact routes for temple goers/workers. For personal extreme exposure to carcinogenic PAH in the temple, 95% probability total ILCR (TILCR) (9.87 x 10(-4) to 1.13 x 10(-3)) is much greater than the range of 10(-6) to 10(-4), indicating high potential health risk to temple workers. For temple goers with high and moderate exposure groups, however, the 95% probability TILCRs were estimated from 6.44 x 10(-5) to 7.50 x 10(-5) and 5.75 x 10(-6) to 6.99 x 10(-6), respectively. This study successfully offers a scientific basis for risk analysis due to incense burning to enhance broad risk management strategies for temple indoor air quality.

  8. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk.

    Science.gov (United States)

    Jonker, Johan W; Merino, Gracia; Musters, Sandra; van Herwaarden, Antonius E; Bolscher, Ellen; Wagenaar, Els; Mesman, Elly; Dale, Trevor C; Schinkel, Alfred H

    2005-02-01

    Contamination of milk with drugs, pesticides and other xenotoxins can pose a major health risk to breast-fed infants and dairy consumers. Here we show that the multidrug transporter BCRP (encoded by ABCG2) is strongly induced in the mammary gland of mice, cows and humans during lactation and that it is responsible for the active secretion of clinically and toxicologically important substrates such as the dietary carcinogen PhIP, the anticancer drug topotecan and the antiulcerative cimetidine into mouse milk.

  9. Technology of Water Purification With Chlorinated Derivatives and Assessment of Risk Associated With Human Exposure to These Substances

    Science.gov (United States)

    Timofeeva, S. S.; Khamidullina, Ye A.; Davydkina, O. A.; Lugovtsova, N. Yu

    2016-04-01

    In the given paper the authors consider the technology of water purification with consideration to the recommendations of the World Health Organization (WHO), European Union (EU) and standards of developed countries. Carcinogenic Unit Risk (UR) magnitude for people constantly exposed to the analyzed carcinogens in the course of a lifetime is estimated. The authors calculate and evaluate unique carcinogenic risk as a complementary probability of cancer development during the whole life of CR when introducing EU standards into water purification technology.

  10. Human health risks associated with residual pesticide levels in edible tissues of slaughtered cattle in Benin City, Southern Nigeria

    Directory of Open Access Journals (Sweden)

    Isioma Tongo

    2015-01-01

    Full Text Available Pesticide residues in meat is of growing concern due to possible adverse effects on humans. Pesticide levels were assessed in five edible cattle parts: muscle, liver, kidney and tongue tissues to determine human health risk associated with consumption of these tissues. Health risk estimates were analysed using estimated daily intake (EDI, hazard quotient (HQ and hazard index (HI for two (2 age/weight categories: 1–11years/30 kg for children while 70 kg was used for adult. Risks were categorized for non-carcinogenic and carcinogenic health effects and measured at the average, maximum, 50th and 95th percentiles of the measured exposure concentrations (MEC. Total pesticide residues ranged from 2.38 to 3.86 μg/kg (muscle, 3.58 to 6.3 μg/kg (liver, 1.87 to 4.59 μg/kg (kidney and 2.54 to 4.35 μg/kg (tongue. Residual pesticide concentrations in the tissues were in the order: Liver > Tongue > Muscle > Kidney. The concentrations of all the assessed pesticides observed in the tissues were however lower than the recommended maximum residual limits (MRLs. Human health risk estimations for the children showed EDI values for heptachlor epoxide, aldrin and dieldrin exceeding threshold values. Non-cancer risk posed to children on consumption of contaminated cattle parts showed HQ values for heptachlor epoxide, aldrin, dieldrin and HI values for organochlorines exceeding 1, indicating the possibility of non-carcinogenic health risks to consumers especially children from consumption of cattle meat from the selected abattoirs.

  11. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  12. Defining molecular and cellular responses after low and high linear energy transfer radiations to develop biomarkers of carcinogenic risk or therapeutic outcome.

    Science.gov (United States)

    Story, Michael; Ding, Liang-hao; Brock, William A; Ang, K Kian; Alsbeih, Ghazi; Minna, John; Park, Seongmi; Das, Amit

    2012-11-01

    The variability in radiosensitivity across the human population is governed in part by genetic factors. The ability to predict therapeutic response, identify individuals at greatest risk for adverse clinical responses after therapeutic radiation doses, or identify individuals at high risk for carcinogenesis from environmental or medical radiation exposures has a medical and economic impact on both the individual and society at large. As radiotherapy incorporates particles, particularly particles larger than protons, into therapy, the need for such discriminators, (i.e., biomarkers) will become ever more important. Cellular assays for survival, DNA repair, or chromatid/chromosomal analysis have been used to identify at-risk individuals, but they are not clinically applicable. Newer approaches, such as genome-wide analysis of gene expression or single nucleotide polymorphisms and small copy number variations within chromosomes, are examples of technologies being applied to the discovery process. Gene expression analysis of primary or immortalized human cells suggests that there are distinct gene expression patterns associated with radiation exposure to both low and high linear energy transfer radiations and that those most radiosensitive are discernible by their basal gene expression patterns. However, because the genetic alterations that drive radio response may be subtle and cumulative, the need for large sample sizes of specific cell or tissue types is required. A systems biology approach will ultimately be necessary. Potential biomarkers from cell lines or animal models will require validation in a human setting where possible and before being considered as a credible biomarker some understanding of the molecular mechanism is necessary.

  13. Noncoding RNA response to xenobiotic exposure: an indicator of toxicity and carcinogenicity.

    Science.gov (United States)

    Marrone, April K; Beland, Frederick A; Pogribny, Igor P

    2014-10-01

    Human exposure to certain environmental and occupational chemicals is one of the major risk factors for noncommunicable diseases, including cancer. Therefore, it is desirable to take advantage of subtle exposure-related adverse cellular events for early disease detection and to identify potential dangers caused by new and currently under-evaluated drugs and chemicals. Nongenotoxic events due to carcinogen/toxicant exposure are a general hallmark of sustained cellular stress leading to tumorigenesis. These processes are globally regulated via noncoding RNAs (ncRNAs). Tumorigenesis-associated genotoxic and nongenotoxic events lead to the altered expression of ncRNAs and may provide a mechanistic link between chemical exposure and tumorigenesis. Current advances in toxicogenomics are beginning to provide valuable insight into gene-chemical interactions at the transcriptome level. In this review, we summarize recent information about the impact of xenobiotics on ncRNAs. Evidence highlighted in this review suggests a critical role of ncRNAs in response to carcinogen/toxicant exposure. Benefits for the use of ncRNAs in carcinogenicity assessment include remarkable tissue specificity, early appearance, low baseline variability, and their presence and stability in biological fluids, which suggests that the incorporation of ncRNAs in the evaluation of cancer risk assessment may enhance substantially the efficiency of toxicity and carcinogenicity testing.

  14. Ecological and human health risks associated with abandoned gold mine tailings contaminated soil

    Science.gov (United States)

    Ngole-Jeme, Veronica Mpode; Fantke, Peter

    2017-01-01

    Gold mining is a major source of metal and metalloid emissions into the environment. Studies were carried out in Krugersdorp, South Africa, to evaluate the ecological and human health risks associated with exposure to metals and metalloids in mine tailings contaminated soils. Concentrations of arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni), and zinc (Zn) in soil samples from the area varied with the highest contamination factors (expressed as ratio of metal or metalloid concentration in the tailings contaminated soil to that of the control site) observed for As (3.5x102), Co (2.8x102) and Ni (1.1x102). Potential ecological risk index values for metals and metalloids determined from soil metal and metalloid concentrations and their respective risk factors were correspondingly highest for As (3.5x103) and Co (1.4x103), whereas Mn (0.6) presented the lowest ecological risk. Human health risk was assessed using Hazard Quotient (HQ), Chronic Hazard Index (CHI) and carcinogenic risk levels, where values of HQ > 1, CHI > 1 and carcinogenic risk values > 1×10−4 represent elevated risks. Values for HQ indicated high exposure-related risk for As (53.7), Cr (14.8), Ni (2.2), Zn (2.64) and Mn (1.67). Children were more at risk from heavy metal and metalloid exposure than adults. Cancer-related risks associated with metal and metalloid exposure among children were also higher than in adults with cancer risk values of 3×10−2 and 4×10−2 for As and Ni respectively among children, and 5×10−3 and 4×10−3 for As and Ni respectively among adults. There is significant potential ecological and human health risk associated with metal and metalloid exposure from contaminated soils around gold mine tailings dumps. This could be a potential contributing factor to a setback in the health of residents in informal settlements dominating this mining area as the immune systems of some of these residents are already

  15. Environmental carcinogens and mutational pathways in atherosclerosis.

    Science.gov (United States)

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A

    2015-05-01

    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms.

  16. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

    Directory of Open Access Journals (Sweden)

    Lygia T Budnik

    Full Text Available There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD but (mostly lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001. The decreased integrity of mtDNA (mtDNA-230/mtDNA-79 in exposed individuals implicates apoptotic processes (p = 0.015. The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001. Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

  17. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

    Science.gov (United States)

    Budnik, Lygia T; Kloth, Stefan; Baur, Xaver; Preisser, Alexandra M; Schwarzenbach, Heidi

    2013-01-01

    There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD) but (mostly) lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment) and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001). The decreased integrity of mtDNA (mtDNA-230/mtDNA-79) in exposed individuals implicates apoptotic processes (p = 0.015). The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001). Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

  18. Improving prediction of carcinogenicity to reduce, refine, and replace the use of experimental animals.

    Science.gov (United States)

    Bourcier, Todd; McGovern, Tim; Stavitskaya, Lidiya; Kruhlak, Naomi; Jacobson-Kram, David

    2015-03-01

    Cancer risk assessment of new pharmaceuticals is crucial to protect public health. However, clinical trials lack the duration needed to clearly detect drug-related tumor emergence, and biomarkers suggestive of increased cancer risk from a drug typically are not measured in clinical trials. Therefore, the carcinogenic potential of a new pharmaceutical is extrapolated predominately based on 2-y bioassays in rats and mice. A key drawback to this practice is that the results are frequently positive for tumors and can be irrelevant to human cancer risk for reasons such as dose, mode of action, and species specificity. Alternative approaches typically strive to reduce, refine, and replace rodents in carcinogenicity assessments by leveraging findings in short-term studies, both in silico and in vivo, to predict the likely tumor outcome in rodents or, more broadly, to identify a cancer risk to patients. Given the complexities of carcinogenesis and the perceived impracticality of assessing risk in the course of clinical trials, studies conducted in animals will likely remain the standard by which potential cancer risks are characterized for new pharmaceuticals in the immediate foreseeable future. However, a weight-of-evidence evaluation based on short-term toxicologic, in silico, and pharmacologic data is a promising approach to identify with reasonable certainty those pharmaceuticals that present a likely cancer risk in humans and, conversely, those that do not present a human cancer risk.

  19. Critical elements for human health risk assessment of less than lifetime exposures.

    Science.gov (United States)

    Geraets, Liesbeth; Nijkamp, Monique M; Ter Burg, Wouter

    2016-11-01

    Less than lifetime exposure has confronted risk assessors as to how to interpret the risks for human health in case a chronic health-based limit is exceeded. Intermittent, fluctuating and peak exposures do not match with the basis of the chronic limit values possibly leading to conservative outcomes. This paper presents guidance on how to deal with human risk assessment of less than lifetime exposure. Important steps to be considered are characterization of the human exposure situation, evaluation whether the human less than lifetime exposure scenario corresponds to a non-chronic internal exposure: toxicokinetic and toxicodynamic considerations, and, finally, re-evaluation of the risk assessment. Critical elements for these steps are the mode of action, Haber's rule, and toxicokinetics (ADME) amongst others. Previous work for the endpoints non-genotoxic carcinogenicity and developmental toxicity is included in the guidance. The guidance provides a way to consider the critical elements, without setting default factors to correct for the less than lifetime exposure in risk assessment.

  20. Carcinogens formed when Meat is Cooked

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Salmon, C P; Knize, M G

    2003-05-30

    Diet has been associated with varying cancer rates in human populations for many years, yet the causes of the observed variation in cancer patterns have not been adequately explained (Wynder et al. 1977). Along with the effect of diet on human cancer incidence is the strong evidence that mutations are the initiating events in the cancer process (Vogelstein et al. 1992). Foods, when heated, are a good source of genotoxic carcinogens that very likely are a cause for some of these events(Doll et al. 1981). These carcinogens fall into two chemical classes: heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH). There is ample evidence that many of these compounds are complete carcinogens in rodents(El-Bayoumy et al. 1995; Ohgaki et al. 1991). Heterocyclic aromatic amines are among the most potent mutagenic substances ever tested in the Ames/Salmonella mutagenicity test (Wakabayashi et al. 1992). Both classes of carcinogen cause tumors in rodents at multiple sites, (El-Bayoumy et al. 1995; Ohgaki et al. 1991) many of which are common tumor sites in people on a Western diet. An HAA, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and a PAH, B[a]P (benzo[a]pyrene), of comparable carcinogenic potency caused mammary gland tumors in a feeding study in female rats (El-Bayoumy et al. 1995). In addition, PhIP has recently been shown to cause carcinomas in the prostate of the male rat (Shirai et al. 1997). Complementing the rodent cancer studies are numerous human case-control and prospective studies suggesting a relationship between overheated beef, chicken, and lamb, and cancer of the colon, breast, prostate, and stomach (Sinha et al. 1999; Ward et al. 1997; Zheng et al. 1998).

  1. Formalized Search Strategies for Human Risk Contributions

    DEFF Research Database (Denmark)

    Rasmussen, Jens; Pedersen, O. M.

    For risk management, the results of a probabilistic risk analysis (PRA) as well as the underlying assumptions can be used as references in a closed-loop risk control; and the analyses of operational experiences as a means of feedback. In this context, the need for explicit definition and document......For risk management, the results of a probabilistic risk analysis (PRA) as well as the underlying assumptions can be used as references in a closed-loop risk control; and the analyses of operational experiences as a means of feedback. In this context, the need for explicit definition...... and documentation of the PRA coverage, including the search strategies applied, is discussed and aids are proposed such as plant description in terms of a formal abstraction hierarchy and use of cause-consequence-charts for the documentation of not only the results of PRA but also of its coverage. Typical human...... risk contributions are described on the basis of general plant design features relevant for risk and accident analysis. With this background, search strategies for human risk contributions are treated: Under the designation "work analysis", procedures for the analysis of familiar, well trained, planned...

  2. Spatial and seasonal variations, sources, air-soil exchange, and carcinogenic risk assessment for PAHs and PCBs in air and soil of Kutahya, Turkey, the province of thermal power plants.

    Science.gov (United States)

    Dumanoglu, Yetkin; Gaga, Eftade O; Gungormus, Elif; Sofuoglu, Sait C; Odabasi, Mustafa

    2017-02-15

    Atmospheric and concurrent soil samples were collected during winter and summer of 2014 at 41 sites in Kutahya, Turkey to investigate spatial and seasonal variations, sources, air-soil exchange, and associated carcinogenic risks of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). The highest atmospheric and soil concentrations were observed near power plants and residential areas, and the wintertime concentrations were generally higher than ones measured in summer. Spatial distribution of measured ambient concentrations and results of the factor analysis showed that the major contributing PAH sources in Kutahya region were the coal combustion for power generation and residential heating (48.9%), and diesel and gasoline exhaust emissions (47.3%) while the major PCB sources were the coal (thermal power plants and residential heating) and wood combustion (residential heating) (45.4%), and evaporative emissions from previously used technical PCB mixtures (34.7%). Results of fugacity fraction calculations indicated that the soil and atmosphere were not in equilibrium for most of the PAHs (88.0% in winter, 87.4% in summer) and PCBs (76.8% in winter, 83.8% in summer). For PAHs, deposition to the soil was the dominant mechanism in winter while in summer volatilization was equally important. For PCBs, volatilization dominated in summer while deposition was higher in winter. Cancer risks associated with inhalation and accidental soil ingestion of soil were also estimated. Generally, the estimated carcinogenic risks were below the acceptable risk level of 10(-6). The percentage of the population exceeding the acceptable risk level ranged from 10(-6). Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Carcinogenicity of azo colorants: influence of solubility and bioavailability.

    Science.gov (United States)

    Golka, Klaus; Kopps, Silke; Myslak, Zdislaw W

    2004-06-15

    In the past, azo colorants based on benzidine, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine (o-tolidine), and 3,3'-dimethoxybenzidine (o-dianisidine) have been synthesized in large amounts and numbers. Studies in exposed workers have demonstrated that the azoreduction of benzidine-based dyes occurs in man. The metabolic conversion of benzidine-, 3,3'-dimethylbenzidine- and 3,3'-dimethoxybenzidine-based dyes to their (carcinogenic) amine precursors in vivo is a general phenomenon that must be considered for each member of this class of chemicals. Several epidemiological studies have demonstrated that the use of the benzidine-based dyes has caused bladder cancer in humans. However, in contrast to water-soluble dyes, the question of biological azoreduction of (practically insoluble) pigments has been a matter of discussion. As a majority of azo pigments are based on 3,3'-dichlorobenzidine, much of the available experimental data are focused on this group. Long-term animal carcinogenicity studies performed with pigments based on 3,3'-dichlorobenzidine did not show a carcinogenic effect. The absence of a genotoxic effect has been supported by mutagenicity studies with the 3,3'-dichlorobenzidine-based Pigment Yellow 12. Studies in which azo pigments based on 3,3'-dichlorobenzidine had been orally administered to rats, hamsters, rabbits and monkeys could generally not detect significant amounts of 3,3'-dichlorobenzidine in the urine. It, therefore, appears well established that the aromatic amine components from azo pigments based on 3,3'-dichlorobenzidine are practically not bioavailable. Hence, it is very unlikely that occupational exposure to insoluble azo pigments would be associated with a substantial risk of (bladder) cancer in man. According to current EU regulations, azo dyes based on benzidine, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine have been classified as carcinogens of category 2 as "substances which should be regarded as if they are carcinogenic

  4. Formaldehyde in dentistry: a review of mutagenic and carcinogenic potential

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, B.B.; Chestner, S.B.

    1981-09-01

    For many years there has been controversy over the value of antimicrobial drugs for intracanal dressings in endodontics. Formocresol, a formaldehyde compound, has evolved as the preferred drug for routine endodontic procedures, as well as pediatric endodontics. The increase in the use of formaldehyde has been complicated by the introduction of paraformaldehyde pastes for filling root canals. Neither of these formulas has ever been standardized. The doses are arbitrary, and the common dose of formocresol has been shown to be many times greater than the minimum dose needed for effect. The efficacy of paraformaldehyde pastes is questionable and remains clouded by inconclusive evidence, conflicting research, inadequate terminology, and a lack of convincing statistical evidence. The clinical use and delivery of formocresol and paraformaldehyde pastes remain arbitrary and unscientific. Formaldehyde has a known toxic mutagenic and carcinogenic potential. Many investigations have been conducted to measure the risk of exposure to formaldehyde; it is clear that formaldehyde poses a carcinogenic risk in humans. There is a need to reevaluate the rationale underlying the use of formaldehyde in dentistry particularly in light of its deleterious effects.

  5. Screening assays for carcinogenic agents and mixtures: an appraisal based on data in the IARC Monograph series.

    Science.gov (United States)

    Bartsch, H; Malaveille, C

    1990-01-01

    To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans and which types of short-term test are more relevant for predicting human hazards, an analysis was performed on agents that were evaluated in IARC Monographs Supplements 6 and 7 for their carcinogenic effects in humans and animals and for activity in short-term genotoxicity tests. The prevalence of genotoxicity among four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 66) was determined. Each of the groups 1, 2A and 2B contained a high proportion (80-90%) of genotoxic carcinogens, which were also multi-species or multi-tissue carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and many in group 3. Although limited by the data-base available through the Monographs series, this analysis implies that genotoxic carcinogens add more to the human cancer burden than non-genotoxic carcinogens. Thus, the continued use of in vitro/in vivo short-term tests, involving as endpoints DNA chromosomal or mutational damage, to identify genotoxic carcinogens or in the isolation of carcinogenic components in complex mixtures is fully justified. It is concluded that (a) an agent or complex mixture with unknown carcinogenic potential showing sufficient evidence of activity in genotoxicity assays in vitro or in vivo is likely to represent a hazard to humans and (b) an agent or complex mixture showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity for rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens.

  6. Tumorigenic effects in Wistar rats orally administered benzo[a] pyrene for two years (gavage studies). Implications for human cancer risks associated with oral exposure to polycyclic aromatic hydrocarbons

    NARCIS (Netherlands)

    Kroese ED; Muller JJA; Mohn GR; Dortant PM; Wester PW; LEO; LPI; CSR

    2002-01-01

    Humans are exposed via the environment and via food to Polycyclic Aromatic Hydrocarbons (PAH), mixtures considered carcinogenic by IARC. A quantitative cancer risk assessment for oral exposure is hampered by the absence of adequate data. The need for experimental data is substantiated by the fact th

  7. Physiologically based kinetic models for the alkenylbenzene elemicin in rat and human and possible implications for risk assessment.

    Science.gov (United States)

    van den Berg, Suzanne J P L; Punt, Ans; Soffers, Ans E M F; Vervoort, Jacques; Ngeleja, Stephen; Spenkelink, Bert; Rietjens, Ivonne M C M

    2012-11-19

    The present study describes physiologically based kinetic (PBK) models for the alkenylbenzene elemicin (3,4,5-trimethoxyallylbenzene) in rat and human, based on the PBK models previously developed for the structurally related alkenylbenzenes estragole, methyleugenol, and safrole. Using the newly developed models, the level of metabolic activation of elemicin in rat and human was predicted to obtain insight in species differences in the bioactivation of elemicin and read across to the other methoxy allylbenzenes, estragole and methyleugenol. Results reveal that the differences between rat and human in the formation of the proximate carcinogenic metabolite 1'-hydroxyelemicin and the ultimate carcinogenic metabolite 1'-sulfoxyelemicin are limited (rat and human liver. The insights thus obtained were used to perform a risk assessment for elemicin using the margin of exposure (MOE) approach and read across to the other methoxy allylbenzene derivatives for which in vivo animal tumor data are available. This reveals that elemicin poses a lower priority for risk management as compared to its structurally related analogues estragole and methyleugenol. Altogether, the results obtained indicate that PBK modeling provides an important insight in the occurrence of species differences in the metabolic activation of elemicin. Moreover, they provide an example of how PBK modeling can facilitate a read across in risk assessment from compounds for which in vivo toxicity studies are available to a compound for which only limited toxicity data have been described, thus contributing to the development of alternatives for animal testing.

  8. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  9. Ecological and human health risks from metal(loid)s in peri-urban soil in Nanjing, China.

    Science.gov (United States)

    Ding, Zhuhong; Hu, Xin

    2014-06-01

    In order to investigate the ecological and human health risks of metal(loid)s (Cu, Pb, Zn, Ni, Cd, Mn, Cr, and As) in peri-urban soils, 43 surface soil samples were collected from the peri-urban area around Nanjing, a megacity in China. The average contents were 1.19, 67.8, 37.6, 105, 167, 44.6, 722, and 50.8 mg kg(-1) for Cd, Cr, Ni, Pb, Zn, Cu, Mn, and As, respectively. A significant positive correlation was found between Cu, Pb, Zn, Cd, Mn, and As (p urban soil samples. Potential ecological risk indices show that the metal(loid)s in the soil could result in higher ecological risks. Cd is the main contributor to the risk, followed by As. The levels of Cu, Pb, Zn, Cd, Mn, and As in stomach and intestinal phases show a positive linear correlation with their total contents. Mn, Zn, Ni, Cd, and Pb in stomach phase showed higher bioaccessibility, while in intestinal phase, Cu, Cr, and As had the higher bioaccessibility. The carcinogenic risk in children and adults posed by As, Pb, and Cr via ingestion was deemed acceptable. The non-carcinogenic risks posed by these metal(loid)s via ingestion to children are higher than to adults and mainly result from As.

  10. Human health risk assessment of heavy metals in tropical fish and shellfish collected from the river Buriganga, Bangladesh.

    Science.gov (United States)

    Ahmed, Md Kawser; Baki, Mohammad Abdul; Islam, Md Saiful; Kundu, Goutam Kumar; Habibullah-Al-Mamun, Md; Sarkar, Santosh Kumar; Hossain, Md Muzammel

    2015-10-01

    Although fish, crustacean, and shellfish are significant sources of protein, they are currently affected by rapid industrialization, resulting in increased concentrations of heavy metals. Accumulation of heavy metals (V, Cr, Mn, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, and Pb) and associated human health risk were investigated in three fish species, namely Ailia coila, Gagata youssoufi, and Mastacembelus pancalus; one crustacean (prawn), Macrobrachium rosenbergii; and one Gastropoda, Indoplanorbis exustus, collected from the Buriganga River, Bangladesh. Samples were collected from the professional fishermen. Cu was the most accumulated metal in M. rosenbergii. Ni, As, Ag, and Sb were in relatively lower concentrations, whereas relatively higher accumulation of Cr, Mn, Zn, and Se were recorded. Mn, Zn, and Pb were present in higher concentrations than the guidelines of various authorities. There were significant differences in metal accumulation among different fish, prawn, or shellfish species. Target hazard quotient (THQ) and target cancer risk (TR) were calculated to estimate the non-carcinogenic and carcinogenic health risks, respectively. The THQ for individual heavy metals were below 1 suggesting no potential health risk. But combined impact, estimated by hazard index (HI), suggested health risk for M. pancalus consumption. Although consumption of fish at current accumulation level is safe but continuous and excess consumption for a life time of more than 70 years has probability of target cancer risk.

  11. Mineral fibre persistence and carcinogenicity.

    Science.gov (United States)

    McDonald, J C

    1998-10-01

    Epidemiological research during the past 40 years has demonstrated with increasing clarity that amphibole asbestos fibres--crocidolite, amosite and tremolite--are more carcinogenic than chrysotile. A smaller number of well-controlled studies using lung burden analyses, while adding to the specificity of this conclusion, have shown that amphibole fibres also differ from chrysotile in being far more durable and biopersistent in lung tissue. Analyses of mesothelioma and lung cancer in a large cohort of Canadian chrysotile miners and millers have recently shown that the low-level presence of fibrous tremolite in these mines, rather than the chrysotile, may well be responsible. The high risk of lung cancer, but not of mesothelioma, in the chrysotile textile industry remains anomalous and cannot be explained in this way. These various findings are directly relevant to the choice of the experimental methods which should be used for screening man-made fibres for industrial use. Although it is clear that biopersistence is a major determinant of cancer risk in animals, and perhaps also in man, other factors affecting the biological activity of mineral fibres may also be important.

  12. PROPOSED PROCEDURE FOR DERIVATION OF REGULATORY VALUES FOR CARCINOGENIC AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) BASED ON COAL TAR PITCH (CTP) VOLATILES

    Science.gov (United States)

    A procedure for estimating upper bound lifetime human cancer risk from air levels of 6 common carcinogenic PAHs, termed "PAHs of concern", is proposed. These PAHs are benzo(a)pyrene, benz(a)anathracene, benzo(k)flouranthene, indeno(1,2,3-c,d)pyrene and chrysene. In application,...

  13. PROPOSED PROCEDURE FOR DERIVATION OF REGULATORY VALUES FOR CARCINOGENIC AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) BASED ON COAL TAR PITCH (CTP) VOLATILES

    Science.gov (United States)

    A procedure for estimating upper bound lifetime human cancer risk from air levels of 6 common carcinogenic PAHs, termed "PAHs of concern", is proposed. These PAHs are benzo(a)pyrene, benz(a)anathracene, benzo(k)flouranthene, indeno(1,2,3-c,d)pyrene and chrysene. In application,...

  14. Report on carcinogens monograph on 1-bromopropane.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

  15. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: relevance to human cancer risk.

    Science.gov (United States)

    Labib, Sarah; Guo, Charles H; Williams, Andrew; Yauk, Carole L; White, Paul A; Halappanavar, Sabina

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mgBaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans.

  16. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.

    Science.gov (United States)

    Herceg, Zdenko; Lambert, Marie-Pierre; van Veldhoven, Karin; Demetriou, Christiana; Vineis, Paolo; Smith, Martyn T; Straif, Kurt; Wild, Christopher P

    2013-09-01

    Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

  17. Emissions during the BHP Billiton mozal aluminium smelter Fume Treatment Centre (FTC) rebuild – A human health perspective

    CSIR Research Space (South Africa)

    Wright, C

    2011-02-01

    Full Text Available some are probable human carcinogens. As a result MOZAL initiated a human health risk assessment (HHRA) study concerning this operation, in order to understand the potential health impacts on the surrounding communities, including Mahlampsene, Sikuama...

  18. Genetic analysis of colon tumors induced by a dietary carcinogen PhIP in CYP1A humanized mice: Identification of mutation of β-catenin/Ctnnb1 as the driver gene for the carcinogenesis.

    Science.gov (United States)

    Wang, Hong; Zhou, Hong; Liu, Anna; Guo, Xiangyi; Yang, Chung S

    2015-11-01

    Replacing mouse Cyp1a with human CYP1A enables the humanized CYP1A mice to mimic human metabolism of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), by N(2) -hydroxylation to a proximate carcinogen. Our previous study demonstrated that PhIP, combined with the dextrin sulfate sodium (DSS)-induced colitis, induces colon carcinogenesis in hCYP1A mice. Here, we employed whole exome sequencing and found multiple gene mutations in PhIP/DSS-induced colon tumors. Mutations in the exon 3 of Ctnnb1/β-catenin, however, were the predominant events. We further sequenced the key fragments of Apc, Ctnnb1, and Kras, because mutations of these genes in the humans are commonly found as the drivers of colorectal cancer. Mutations on either codon 32 or 34 in the exon 3 of Ctnnb1 were found in 39 out of 42 tumors, but no mutation was found in either Apc or Kras. The sequence context of codons 32 and 34 suggests that PhIP targets +3G in a TGGA motif of Ctnnb1. Since mutations that activate Wnt signal is a major driving force for human colorectal cancers, we conclude that the mutated β-catenin is the driver in PhIP/DSS-induced colon carcinogenesis. This result suggests that the colon tumors in hCYP1A mice mimic human colorectal carcinogenesis not only in the dietary etiology involving PhIP, but also in the aberrant activation of the Wnt signaling pathway as the driving force.

  19. Potential health effects of exposure to carcinogenic compounds in incense smoke in temple workers.

    Science.gov (United States)

    Navasumrit, Panida; Arayasiri, Manasawee; Hiang, Ohmar May Tin; Leechawengwongs, Manoon; Promvijit, Jeerawan; Choonvisase, Suppachai; Chantchaemsai, Samroeng; Nakngam, Netnapa; Mahidol, Chulabhorn; Ruchirawat, Mathuros

    2008-05-09

    Incense smoke is a potential hazard to human health due to various airborne carcinogens emitted from incense burning. This study aimed to evaluate the potential health effects of exposure to benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) emitted from incense smoke in temple workers. Exposure and health risks were assessed through the measurement of ambient exposure as well as through the use of biomarkers of exposure and early biological effects. Ambient air measurement showed that incense burning generates significantly higher levels of airborne benzene (Pincense burning may increase health risk for the development of cancer in temple workers.

  20. Conversion of Suspected Food Carcinogen 5-Hydroxymethylfurfural by Sulfotransferases and Aldehyde Dehydrogenases in Postmitochondrial Tissue Preparations of Humans, Mice, and Rats.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

    2016-01-01

    The food contaminant 5-hydroxymethylfurfural (HMF) is formed by heat- and acid-catalyzed reactions from carbohydrates. More than 80% of HMF is metabolized by oxidation of the aldehyde group in mice and rats. Sulfo conjugation yields mutagenic 5-sulfoxymethylfurfural, the probable cause for the neoplastic effects observed in HMF-treated rodents. Considerable metabolic differences between species hinder assessing the tumorigenic risk associated with human dietary HMF uptake. Here, we assayed HMF turnover catalyzed by sulfotransferases or by aldehyde dehydrogenases (ALDHs) in postmitochondrial preparations from liver, kidney, colon, and lung of humans, mice, and rats. The tissues-specific clearance capacities of HMF sulfo conjugation (CL(SC)) and ALDH-catalyzed oxidation (CL(OX)) were concentrated to the liver. The hepatic clearance CL(SC) in mice (males: 487 µl/min/kg bw, females: 2520 µl/min/kg bw) and rats (males: 430 µl/min/kg bw, females: 198 µl/min/kg bw) were considerably higher than those in humans (males: 21.2 µl/min/kg bw, females: 32.2 µl/min/kg bw). The ALDH-related clearance rates CLOX in mice (males: 3400 ml/min/kg bw, females: 1410 ml/min/kg bw) were higher than those of humans (males: 436 ml/min/kg bw, females: 646 ml/min/kg bw) and rats (males: 627 ml/min/kg bw, females: 679 ml/min/kg bw). The ratio of CL(OX) to CL(SC) was lowest in female mice. This finding indicated that HMF sulfo conjugation was most substantial in the liver of female mice, a target tissue for HMF-induced neoplastic effects, and that humans may be less sensitive regarding HMF sulfo conjugation compared with the rodent models.

  1. Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage

    DEFF Research Database (Denmark)

    Hagmar, L; Brøgger, A; Hansteen, I L;

    1994-01-01

    Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively to survey the exposure of humans to genotoxic agents. The conceptual basis for this has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target...... tissues. Until now, no follow-up studies have been performed to assess the predictive value of these methods for subsequent cancer risk. In an ongoing Nordic cohort study of cancer incidence, 3182 subjects were examined between 1970 and 1988 for chromosomal aberrations (CA), sister chromatid exchange.......0009) in CA strata with regard to subsequent cancer risk. The point estimates of the standardized incidence ratio in the three CA strata were 0.9, 0.7, and 2.1, respectively. Thus, an increased level of chromosome breakage appears to be a relevant biomarker of future cancer risk....

  2. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    Science.gov (United States)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  3. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    Science.gov (United States)

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

  4. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  5. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  6. Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure.

    Science.gov (United States)

    Maronpot, R R; Thoolen, R J M M; Hansen, B

    2015-02-01

    Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin.

  7. Human Plague Risk: Spatial-Temporal Models

    Science.gov (United States)

    Pinzon, Jorge E.

    2010-01-01

    This chpater reviews the use of spatial-temporal models in identifying potential risks of plague outbreaks into the human population. Using earth observations by satellites remote sensing there has been a systematic analysis and mapping of the close coupling between the vectors of the disease and climate variability. The overall result is that incidence of plague is correlated to positive El Nino/Southem Oscillation (ENSO).

  8. Quantification of decreasing of human health risk by bioremediation of a contaminated soil with petroleum hydrocarbons; Quantificacao do decrescimo de risco associado a biorremediacao de um solo contaminado por hidrocarbonetos de petroleo

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Cristiane A.; Castilhos, Zuleica C.; Rizzo, Andrea C.L. [Centro de Tecnologia Mineral (CETEM), Rio de Janeiro, RJ (Brazil); Leite, Selma G.F. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Escola de Quimica

    2004-07-01

    The main objective of this work was to evaluate the efficiency of four different bioremediation processes in the decrease of organic pollutants present in a soil contaminated with crude oil, using a toxicological approach based on the human health risk assessment methodology (USEPA, 1989). The different techniques of bioremediation utilized (biostimulation, bioaugmentation and addition of enzymatic solution) were efficient in the removal of the organic pollutants, especially of PAHs, considered highly recalcitrant. In the human health risk assessment, the exposure pathway that resulted in higher hazards of no-carcinogenic effects and risks of carcinogenic effects in the population (children and adult) was dermal contact with soil. The pollutant that contributed more in the different exposure pathways was benzo(a)pyrene. When carcinogenic and no-carcinogenic effects in children and adults were evaluated, the different treatments showed efficiency, once they were capable to reduce the risk and the hazard index (HI) bellow target levels (< 1 x 10{sup -4} and 1, respectively), showing that these treatments were efficient to decrease the potential damage in the exposed population. (author)

  9. Acute marijuana effects on human risk taking.

    Science.gov (United States)

    Lane, Scott D; Cherek, Don R; Tcheremissine, Oleg V; Lieving, Lori M; Pietras, Cythia J

    2005-04-01

    Previous studies have established a relationship between marijuana use and risky behavior in natural settings. A limited number of laboratory investigations of marijuana effects on human risk taking have been conducted. The present study was designed to examine the acute effects of smoked marijuana on human risk taking, and to identify behavioral mechanisms that may be involved in drug-induced changes in the probability of risky behavior. Using a laboratory measure of risk taking designed to address acute drug effects, 10 adults were administered placebo cigarettes and three doses of active marijuana cigarettes (half placebo and half 1.77%; 1.77%; and 3.58% Delta9-THC) in a within-subject repeated-measures experimental design. The risk-taking task presented subjects with a choice between two response options operationally defined as risky and nonrisky. Data analyses examined cardiovascular and subjective effects, response rates, distribution of choices between the risky and nonrisky option, and first-order transition probabilities of trial-by-trial data. The 3.58% THC dose increased selection of the risky response option, and uniquely shifted response probabilities following both winning and losing outcomes following selection of the risky option. Acute marijuana administration thereby produced measurable changes in risky decision making under laboratory conditions. Consistent with previous risk-taking studies, shifts in trial-by-trial response probabilities at the highest dose suggested a change in sensitivity to both reinforced and losing risky outcomes. Altered sensitivity to consequences may be a mechanism in drug-induced changes in risk taking. Possible neurobiological sites of action related to THC are discussed.

  10. [Fiber as a carcinogenic agent].

    Science.gov (United States)

    Pott, F

    1987-04-01

    According to the findings that long, thin, and durable fibres have a high carcinogenic potency after intrapleural and intraperitoneal administration, the elongated shape of a particle represents a carcinogenic agent; this physical phenomenon is a special cause of cancer. It induces a biological process which can lead to cancer by several as yet unknown steps. However, the properties of the material the fibres are made of determine the carcinogenic potency of a fibre in a secondary way although they do not seem to be responsible for the true carcinogenic agent. For example, these properties determine the degree of solubility and flexibility. The persistence of fibres in the tissue is a very important property with regard to their carcinogenic effect because the formation of a tumour takes many years or some decades. It can be assumed that a fibre has to remain by the bronchial or serosa tissue until the induction of tumour cells occurs. If this hypothesis is correct, there could be a "durability threshold value" for fibres whose length and diameter would otherwise indicate a high carcinogenic potency. There are indications that other fibre properties apart from length, diameter and durability are important for tumour induction, however, at present, they cannot be included in a definition of carcinogenic fibres. It is proposed to classify all natural and man-made mineral fibres with an aspect ratio of greater than 5:1 as carcinogenic when they are longer than 3 microns, thinner than 1 micron (or can split into such fine fibres) and when they can persist in the tissue for more than 3 years.

  11. Assessment of heavy metal pollution and human health risk in urban soils of steel industrial city (Anshan), Liaoning, Northeast China.

    Science.gov (United States)

    Qing, Xiao; Yutong, Zong; Shenggao, Lu

    2015-10-01

    The purpose of this study was to determine the concentrations and health risk of heavy metals in urban soils from a steel industrial district in China. A total of 115 topsoil samples from Anshan city, Liaoning, Northeast China were collected and analyzed for Cr, Cd, Pb, Zn, Cu, and Ni. The geoaccumulation index (Igeo), pollution index (PI), and potential ecological risk index (PER) were calculated to assess the pollution level in soils. The hazard index (HI) and carcinogenic risk (RI) were used to assess human health risk of heavy metals. The average concentration of Cr, Cd, Pb, Zn, Cu, and Ni were 69.9, 0.86, 45.1, 213, 52.3, and 33.5mg/kg, respectively. The Igeo and PI values of heavy metals were in the descending order of Cd>Zn>Cu>Pb>Ni>Cr. Higher Igeo value for Cd in soil indicated that Cd pollution was moderate. Pollution index indicated that urban soils were moderate to highly polluted by Cd, Zn, Cu, and Pb. The spatial distribution maps of heavy metals revealed that steel industrial district was the contamination hotspots. Principal component analysis (PCA) and matrix cluster analysis classified heavy metals into two groups, indicating common industrial sources for Cu, Zn, Pb, and Cd. Matrix cluster analysis classified the sampling sites into four groups. Sampling sites within steel industrial district showed much higher concentrations of heavy metals compared to the rest of sampling sites, indicating significant contamination introduced by steel industry on soils. The health risk assessment indicated that non-carcinogenic values were below the threshold values. The hazard index (HI) for children and adult has a descending order of Cr>Pb>Cd>Cu>Ni>Zn. Carcinogenic risks due to Cr, Cd, and Ni in urban soils were within acceptable range for adult. Carcinogenic risk value of Cr for children is slightly higher than the threshold value, indicating that children are facing slight threat of Cr. These results provide basic information of heavy metal pollution control

  12. Epidemiologic approaches to assessing human cancer risk from consuming aquatic food resources from chemically contaminated water

    Energy Technology Data Exchange (ETDEWEB)

    Ozonoff, D. (Boston Univ. School of Public Health, MA (United States)); Longnecker, M.P. (UCLA School of Public Health, Los Angeles, CA (United States))

    1991-01-01

    Epidemiologic approaches to assessing human cancer risk from contaminated waters must confront the problems of long latency and rarity of the end point (cancer). The latency problem makes determination of diet history more difficult, while the low frequency of cancer as an end point reduces the statistical power of the study. These factors are discussed in relation to the study designs most commonly employed in epidemiology. It is suggested that the use of biomarkers for persistent chemicals may be useful to mitigate the difficulty of determining exposure, while the use of more prevalent and timely end points, such as carcinogen-DNA adducts or oncogene proteins, may make the latency and rarity problems more tractable.

  13. Report on carcinogens monograph on cumene.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

  14. Quantification of carcinogenic 4- to 6-ring polycyclic aromatic hydrocarbons in human urine by solid-phase microextraction gas chromatography-isotope dilution mass spectrometry.

    Science.gov (United States)

    Campo, Laura; Fustinoni, Silvia; Bertazzi, Pieralberto

    2011-08-01

    Polycyclic aromatic hydrocarbons (PAHs) are pollutants found in living and working environments. The aim of this study was to develop a solid-phase microextraction (SPME) gas chromatography (GC)-isotope dilution mass spectrometry method for the quantification of 10 four- to six-ring PAHs in urine samples. Seven of the selected PAHs have been classified as carcinogenic. Under the final conditions, analytes were sampled with a 100-μm polydimethylsiloxane SPME fibre for 60 min at 80 °C and desorbed in the injection port of the GC at 270 °C. Fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, indeno[1,2,3-cd]pyrene and benzo[ghi]perylene were separated using a highly arylene-modified phase capillary column and quantified by MS using eight deuterated PAHs as surrogate internal standards. Limits of quantification (LOQ) were in the 0.5- to 2.2-ng/L range. Validation showed linear dynamic ranges up to 340 ng/L, inter- and intra-run precisions <20%, and accuracies within 20% of spiked concentrations. Matrix effect evaluation and the use of control charts to monitor process performances showed that the isotope dilution approach allowed for the control of bias sources. Urinary PAHs were above or equal to LOQ, depending on different compounds, in 58-100% (min-max), 40-100% and 5-39% of samples from coke oven workers (n = 12), asphalt workers (n = 10) and individuals not occupationally exposed to PAHs (n = 18), respectively. Chrysene was the most abundant PAH determined with median levels of 62.6, 6.9 and <0.6 ng/L, respectively. These results show that the method is suitable for quantifying carcinogenic PAHs in specimens from individuals with different levels of PAH exposure.

  15. Source contribution and risk assessment of airborne toxic metals by neutron activation analysis in Taejeon industrial complex area - Concentration analysis and health risk assessment of airborne toxic metals in Taejeon 1,2 industrial Complex

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. H.; Jang, M. S.; Nam, B. H.; Yun, M. J. [Chungnam National Univ., Taejeon (Korea)

    2000-04-01

    The study centers on one-year continual concentration analysis using ICP-MS and on health risk assessment of 15 airborne toxic metals in Taejeon 1,2 industrial complex. About 1-year arithmetic mean of human carcinogen, arsenic, hexavalent chromium and nickel subsulfide is 6.05, 2.40 and 2.81 ng/m{sup 3} while the mean of probable human carcinogen, beryllium, cadmium and lead is 0.06, 3.92, 145.99 ng/m{sup 3}, respectively. And the long-term arithmetic mean concentration of non-carcinogenic metal, manganese is 44.60 ng/m{sup 3}. The point risk estimate for the inhalation of carcinogenic metals is 7.0 X10{sup -5}, which is higher than a risk standard of 10{sup -5}. The risk from human carcinogens is 6.2X10{sup -5}, while that from probable human carcinogens is 8.0X10{sup -6}, respectively. About 86 % of the cancer risk is due to the inhalation of human carcinogens, arsenic and hexavalent chromium. Thus, it is necessary to properly manage both arsenic and hexavalent chromium risk in Taejeon 1,2 industrial complex. 37 refs., 13 figs., 9 tabs. (Author)

  16. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish.

    Science.gov (United States)

    Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

    2014-07-30

    Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment.

  17. Evaluating the Impact of Contaminant Dilution and Biodegradation in Uncertainty Quantification of Human Health Risk

    Science.gov (United States)

    Zarlenga, Antonio; de Barros, Felipe; Fiori, Aldo

    2016-04-01

    covariance shape, reaction parameters pertaining to aerobic and anaerobic degradation processes respectively as well as the dose response parameters. Even though the final result assumes a relatively simple form, few numerical quadratures are required in order to evaluate the trajectory moments of the solute plume. In order to perform a sensitivity analysis we apply the methodology to a hypothetical case study. The scenario investigated is made by an aquifer which constitutes a water supply for a population where a continuous source of NAPL contaminant feeds a steady plume. The risk analysis is limited to carcinogenic compounds for which the well-known linear relation for human risk is assumed. Analysis performed shows few interesting findings: the risk distribution is strictly dependent on the pore scale dynamics that trigger dilution and mixing; biodegradation may involve a significant reduction of the risk.

  18. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis.

    Science.gov (United States)

    Smith, Martyn T; Guyton, Kathryn Z; Gibbons, Catherine F; Fritz, Jason M; Portier, Christopher J; Rusyn, Ivan; DeMarini, David M; Caldwell, Jane C; Kavlock, Robert J; Lambert, Paul F; Hecht, Stephen S; Bucher, John R; Stewart, Bernard W; Baan, Robert A; Cogliano, Vincent J; Straif, Kurt

    2016-06-01

    A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volume 100, parts A-F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens. IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor-mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply. We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA's Integrated Risk Information System Program and the U.S. National Toxicology Program. Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K. 2016. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health

  19. Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis

    Science.gov (United States)

    Smith, Martyn T.; Guyton, Kathryn Z.; Gibbons, Catherine F.; Fritz, Jason M.; Portier, Christopher J.; Rusyn, Ivan; DeMarini, David M.; Caldwell, Jane C.; Kavlock, Robert J.; Lambert, Paul F.; Hecht, Stephen S.; Bucher, John R.; Stewart, Bernard W.; Baan, Robert A.; Cogliano, Vincent J.; Straif, Kurt

    2015-01-01

    Background: A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volume 100, parts A–F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens. Objectives and Methods: IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens. Discussion: These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor-mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply. Conclusion: We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA’s Integrated Risk Information System Program and the U.S. National Toxicology Program. Citation: Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K. 2016. Key characteristics of carcinogens as a

  20. A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

    Science.gov (United States)

    Williams, Gary M; Aardema, Marilyn; Acquavella, John; Berry, Sir Colin; Brusick, David; Burns, Michele M; de Camargo, Joao Lauro Viana; Garabrant, David; Greim, Helmut A; Kier, Larry D; Kirkland, David J; Marsh, Gary; Solomon, Keith R; Sorahan, Tom; Roberts, Ashley; Weed, Douglas L

    2016-09-01

    The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

  1. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Hung [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China); Chou, Pei-Hsin [Department of Environmental Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)

    2014-07-30

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  2. Does the term carcinogen send the wrong message?

    Science.gov (United States)

    Flamm, W G; Hughes, D

    1997-08-19

    The term carcinogen has been used by scientists and health regulatory officials for decades. During the last 20 years there have been attempts to redefine the term to make it more rigorous. But, as predicted two decades ago by a benchmark-setting subcommittee of the National Cancer Advisory Board, advances in scientific understanding have brought about dramatic changes in the way we are able to view the term carcinogen. These changes, their scientific bases and their effect on defining the term carcinogen are described. An alternative to the use of the term carcinogen is suggested by the recently proposed US Environmental Agency's guidelines for cancer risk assessment which appear to be in accord with current scientific understanding and the importance of considering the factors affecting the term carcinogen. The guidelines set forth four questions, the answers to which could, in our judgment, replace the need to define or use the term carcinogen which, in light of new scientific knowledge, has become more misleading than useful.

  3. Evaluating the risk of liver cancer in humans exposed in trichloroethylene using physiological models

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, J.W. (Armstrong Lab., Wright-Patterson AFB, OH (United States)); Allen, B.C. (Clement Assoc., Ruston, LA (United States))

    1993-02-01

    Trichloroethylene (TCE) is a widespread environmental pollutant. TCE is classified as a rodent carcinogen by the U.S. Environmental Protection Agency (EPA). Using the rodent cancer bioassay findings and estimates of metabolized dose, the SPA has estimated lifetime exposure cancer risks for humans that ingest TCE in drinking water or inhale TCE. In this study, a physiologically based pharmacokinetic (PB-PK) model for mice was used to simulate selected gavage and inhalation bioassays with TCE. Plausible dose-metrics thought to be linked with the mechanism of action for TCE carcinogenesis were selected. These dose-metrics, adjusted to reflect an average amount per day for a lifetime, were metabolism of TCE (AMET, mg/kg/day) and systemic concentration of TCA (AUCTCA, mg/L/day). These dose-metrics were then used in a linearized multistage model to estimate AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million in mice. A human PB-PK model for TCE was then used to predict TCE concentrations in drinking water and air that would provide AMET and AUCTCA values equal to the predicted mice AMET and AUCTCA values that correspond to liver cancer risks of 1 in 1 million. For the dose-metrics, AMET and AUCTCA, the TCE concentrations in air wave 10.0 and 0.1 ppb TCE (continuous exposure), respectively, and in water, 7 and 4 [mu] TCE/L, respectively.

  4. Human Lung Cancer Risks from Radon – Part I - Influence from Bystander Effects - A Microdose Analysis

    Science.gov (United States)

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2010-01-01

    Since the publication of the BEIR VI report in 1999 on health risks from radon, a significant amount of new data has been published showing various mechanisms that may affect the ultimate assessment of radon as a carcinogen, at low domestic and workplace radon levels, in particular the Bystander Effect (BE) and the Adaptive Response radio-protection (AR). We analyzed the microbeam and broadbeam alpha particle data of Miller et al. (1995, 1999), Zhou et al. (2001, 2003, 2004), Nagasawa and Little (1999, 2002), Hei et al. (1999), Sawant et al. (2001a) and found that the shape of the cellular response to alphas is relatively independent of cell species and LET of the alphas. The same alpha particle traversal dose response behavior should be true for human lung tissue exposure to radon progeny alpha particles. In the Bystander Damage Region of the alpha particle response, there is a variation of RBE from about 10 to 35. There is a transition region between the Bystander Damage Region and Direct Damage Region of between one and two microdose alpha particle traversals indicating that perhaps two alpha particle “hits” are necessary to produce the direct damage. Extrapolation of underground miners lung cancer risks to human risks at domestic and workplace levels may not be valid. PMID:21731539

  5. Urinary Metabolites of the Dietary Carcinogen PhIP are Predictive of Colon DNA Adducts After a Low Dose Exposure in Humans

    Energy Technology Data Exchange (ETDEWEB)

    Malfatti, M; Dingley, K; Nowell, S; Ubick, E; Mulakken, N; Nelson, D; Lang, N; Felton, J; Turteltaub, K

    2006-04-28

    Epidemiologic evidence indicates that exposure to heterocyclic amines (HAs) in the diet is an important risk factor for the development of colon cancer. Well-done cooked meats contain significant levels of HAs which have been shown to cause cancer in laboratory animals. To better understand the mechanisms of HA bioactivation in humans, the most mass abundant HA, 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was used to assess the relationship between PhIP metabolism and DNA adduct formation. Ten human volunteers were administered a dietary relevant dose of [{sup 14}C]PhIP 48-72 h prior to surgery to remove colon tumors. Urine was collected for 24 h after dosing for metabolite analysis, and DNA was extracted from colon tissue and analyzed by accelerator mass spectrometry for DNA adducts. All ten subjects were phenotyped for CYP1A2, NAT2, and SULT1A1 enzyme activity. Twelve PhIP metabolites were detected in the urine samples. The most abundant metabolite in all volunteers was N-hydroxy-PhIP-N{sup 2}-glucuronide. Metabolite levels varied significantly between the volunteers. Interindividual differences in colon DNA adducts levels were observed between each individual. The data showed that individuals with a rapid CYP1A2 phenotype and high levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide, had the lowest level of colon PhIP-DNA adducts. This suggests that glucuronidation plays a significant role in detoxifying N-hydroxy-PhIP. The levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide were negatively correlated to colon DNA adduct levels. Although it is difficult to make definite conclusions from a small data set, the results from this pilot study have encouraged further investigations using a much larger study group.

  6. CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies.

    Science.gov (United States)

    Ma, Qiang; Lu, Anthony Y H

    2007-07-01

    CYP1A1 and 1A2 play critical roles in the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines/amides (HAAs), respectively, to electrophilic reactive intermediates, leading to toxicity and cancer. CYP1As are highly inducible by PAHs and halogenated aromatic hydrocarbons via aryl hydrocarbon receptor-mediated gene transcription. The impact of CYP1A induction on the carcinogenic and toxic potentials of environmental, occupational, dietary, and therapeutic chemicals has been a central focus of human risk evaluation and has broadly influenced the fields of cancer research, toxicology, pharmacology, and risk assessment over the past half-century. From the early discovery of CYP1A induction and its role in protection against chemical carcinogenesis in intact animals, to the establishment of CYP1A enzymes as the principal cytochromes P450 for bioactivation of PAHs and HAAs in in vitro assays, to the recent realization of an essential protective role of CYP1A in benzo[a]pyrene-induced lethality and carcinogenesis with CYP1A knockout mice, the understanding of the interrelation between CYP1A induction and chemical safety has followed a full circle. This unique path of CYP1A research underscores the importance of whole animal and human studies in chemical safety evaluation.

  7. Occurrence, sources, and potential human health risks of polycyclic aromatic hydrocarbons in agricultural soils of the coal production area surrounding Xinzhou, China.

    Science.gov (United States)

    Zhao, Long; Hou, Hong; Shangguan, Yuxian; Cheng, Bin; Xu, Yafei; Zhao, Ruifen; Zhang, Yigong; Hua, Xiaozan; Huo, Xiaolan; Zhao, Xiufeng

    2014-10-01

    A comprehensive investigation of the levels, distribution patterns, and sources of polycyclic aromatic hydrocarbons (PAHs) in agricultural soils of the coal production area surrounding Xinzhou, China, was conducted, and the potential human health risks associated with the levels observed were addressed. A total of 247 samples collected from agricultural soils from the area were analyzed for sixteen PAHs, including highly carcinogenic isomers. The PAH concentrations had a range of n.d. to 782ngg(-1), with a mean value of 202ngg(-1). The two-three ring PAHs were the dominant species, making up 60 percent of total PAHs. Compared with the pollution levels and carcinogenic potential risks reported in other studies, the soil PAH concentrations in the study area were in the low to intermediate range. A positive matrix factorization model indicates that coal/biomass combustion, coal and oil combustion, and coke ovens are the primary PAH sources, accounting for 33 percent, 26 percent, and 24 percent of total PAHs, respectively. The benzo[a]pyrene equivalent (BaPeq) concentrations had a range of n.d. to 476ngg(-1) for PAH7c, with a mean value of 34ngg(-1). The BaPeq concentrations of PAH7c accounted for more than 99 percent of the ∑PAH16, which suggests that seven PAHs were major carcinogenic contributors of ∑PAH16. According to the Canadian Soil Quality Guidelines, only six of the soil samples had concentrations above the safe BaPeq value of 600ngg(-1); the elevated concentrations observed at these sites can be attributed to coal combustion and industrial activities. Exposure to these soils through direct contact probably poses a significant risk to human health as a result of the carcinogenic effects of PAHs. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Protein adducts of the prostate carcinogen PhIP in children

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence Livermore National Laboratory

    2004-02-20

    Prostate cancer is the second leading cause of cancer death in men in the United States. few epidemiology studies have indicated that exposure to PhIP, a rodent prostate carcinogen formed in meat during cooking, may be an important risk factor for prostate cancer in humans. Therefore, a highly sensitive biomarker assay is urgently needed to clarify the role of PhIP in prostate cancer. The goal of this project is to develop an assay that can be used to more accurately quantify human exposure to PhIP and potential prostate cancer risk. Our hypothesis is that an Accelerator Mass Spectrometry-based method can be developed to measure protein adducts of PhIP in the blood of humans. This will provide a measure of the internal dose, as well as the capacity for carcinogen bioactivation to a form that can initiate the cancer process. Towards this goal, we have characterized an adduct formed by PhIP in vitro with the amino acid cysteine. This adduct should provide a biomarker of dietary PhIP exposure and potential prostate cancer risk that could be used to identify individuals for prevention and for monitoring the effect chemoprevention strategies.

  9. Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure.

    OpenAIRE

    Perera, F.; Brennan, T. (Thomas); Fouts, J. R.

    1989-01-01

    There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. Our review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twen...

  10. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the huma

  11. A pesticide monitoring survey in rivers and lakes of northern Greece and its human and ecotoxicological risk assessment.

    Science.gov (United States)

    Papadakis, Emmaluel N; Vryzas, Zisis; Kotopoulou, Athena; Kintzikoglou, Katerina; Makris, Konstantinos C; Papadopoulou-Mourkidou, Euphemia

    2015-06-01

    A pesticide monitoring study covering the main rivers and lakes of Northern Greece (Macedonia, Thrace and Thessaly) was undertaken. A total of 416 samples were collected over a 1.5-year sampling period (September 1999- February 2001) from six rivers and ten lakes. The water samples were analyzed with an off-line solid phase extraction technique coupled with a gas chromatography ion trap mass spectrometer using an analytical method for 147 pesticides and their metabolites, including organochlorines, organophosphates, triazines, chloroacetanilides, pyrethroids, carbamates, phthalimides and other pesticides (herbicides, insecticides and fungicides). Based on the pesticide survey results, a human health carcinogenic and non-carcinogenic risk assessment was conducted for adults and children. Ecotoxicological risk assessment was also conducted using default endpoint values and the risk quotient method. Results showed that the herbicides metolachlor, prometryn, alachlor and molinate, were the most frequently detected pesticides (29%, 12.5%, 12.5% and 10%, respectively). They also exhibited the highest concentration values, often exceeding 1 μg/L. Chlorpyrifos ethyl was the most frequently detected insecticide (7%). Seasonal variations in measured pesticide concentrations were observed in all rivers and lakes. The highest concentrations were recorded during May-June period, right after pesticide application. Concentrations of six pesticides were above the maximum allowable limit of 0.1 μg/L set for drinking water. Alachlor, atrazine and a-HCH showed unacceptable carcinogenic risk estimates (4.5E-06, 4.6E-06 and 1.3E-04, respectively). Annual average concentrations of chlorpyriphos ethyl (0.031 μg L), dicofol (0.01 μg/L), dieldrin (0.02 μg/L) and endosulfan a (0.065 μg/L) exceeded the EU environmental quality standards. The risk quotient estimates for the insecticides chorpyrifos ethyl, diazinon and parathion methyl and herbicide prometryn were above acceptable risk

  12. Phthalates in dormitory and house dust of northern Chinese cities: Occurrence, human exposure, and risk assessment.

    Science.gov (United States)

    Li, Hai-Ling; Song, Wei-Wei; Zhang, Zi-Feng; Ma, Wan-Li; Gao, Chong-Jing; Li, Jia; Huo, Chun-Yan; Mohammed, Mohammed O A; Liu, Li-Yan; Kannan, Kurunthachalam; Li, Yi-Fan

    2016-09-15

    Phthalates are widely used chemicals in household products, which severely affect human health. However, there were limited studies emphasized on young adults' exposure to phthalates in dormitories. In this study, seven phthalates were extracted from indoor dust that collected in university dormitories in Harbin, Shenyang, and Baoding, in the north of China. Dust samples were also collected in houses in Harbin for comparison. The total concentrations of phthalates in dormitory dust in Harbin and Shenyang samples were significantly higher than those in Baoding samples. The total geometric mean concentration of phthalates in dormitory dust in Harbin was lower than in house dust. Di-(2-ethylhexyl) phthalate (DEHP) was the most abundant phthalate in both dormitory and house dust. The daily intakes of the total phthalates, carcinogenic risk (CR) of DEHP, hazard index (HI) of di-isobutyl phthalate (DiBP), dibutyl phthalate (DBP), and DEHP were estimated, the median values for all students in dormitories were lower than adults who live in the houses. Monte Carlo simulation was applied to predict the human exposure risk of phthalates. HI of DiBP, DBP, and DEHP was predicted according to the reference doses (RfD) provided by the United States Environmental Protection Agency (U.S.EPA) and the reference doses for anti-androgenicity (RfD AA) developed by Kortenkamp and Faust. The results indicated that the risks of some students had exceeded the limitation, however, the measured results were not exceeded the limitation. Risk quotients (RQ) of DEHP were predicted based on China specific No Significant Risk Level (NSRL) and Maximum Allowable Dose Level (MADL). The predicted results of CR and RQ of DEHP suggested that DEHP could pose a health risk through intake of indoor dust.

  13. Human exposure risk to heavy metals through groundwater used for drinking in an intensively irrigated river delta

    Science.gov (United States)

    Vetrimurugan, E.; Brindha, K.; Elango, L.; Ndwandwe, Osman Muzi

    2016-09-01

    Drinking water containing heavy metals above the maximum permissible limits cause potential risk to human health. The aim of this study was to determine the groundwater suitability for drinking use based on heavy metal concentration and the associated human exposure risk in an intensively irrigated part of the Cauvery river basin, Tamil Nadu, India. Sixteen heavy metals analysed were in the order of dominance of chromium water quality, and silver, lead and nickel were above limits in all the groundwater samples. In less than 50 % of the groundwater samples, aluminium, boron, cadmium, copper, iron and manganese exceeded their individual permissible limits. Heavy metal pollution index based on 11 heavy metals indicated that groundwater quality of this area is poor-to-unsuitable. Non-carcinogenic risk for humans due to ingestion of groundwater through drinking water pathway was very high for infants, children and adults. Silver, lead, nickel, cadmium and manganese largely contributed to the health hazard. Sources of heavy metals were identified to be geological and from human activities, i.e., application of fertilizers in agricultural fields, seawater intrusion due to intensive pumping for agriculture and wastewater from industries. Groundwater and surface water in this area pose large threat due to high levels of heavy metals, and it is necessary to avoid this water for drinking due to potential risk of health hazard. This study also demonstrated the application of HPI and human exposure hazard index to study the groundwater quality based on heavy metals' concentration.

  14. Chrysotile, tremolite and carcinogenicity.

    Science.gov (United States)

    McDonald, J C; McDonald, A D

    1997-12-01

    It has been suspected for many years that amphibole fibres in the tremolite series, a low level contaminant of chrysotile asbestos, may contribute disproportionately to the incidence of mesothelioma and perhaps other exposure-related cancers. A cohort of some 11,000 Quebec chrysotile workers, 80% of whom have now died, provided the opportunity to examine this hypothesis further. An analysis was made of deaths from mesothelioma (21), cancers of the lung (262), larynx (15), stomach (99), and colon and rectum (76), in men employed by the largest company in Thetford Mines, with closely matched referents. Risks were estimated by logistic regression for these five cancers in two groups of mines--five mines located centrally and ten mines located peripherally; tremolite contamination had been demonstrated to be some four times higher in the former than in the latter. Odds ratios for work in the central mines were raised substantially and significantly for mesothelioma and lung cancer, but not for the gastric, intestinal or laryngeal cancer sites. In the peripheral mines, there was little or no evidence of increased risk for any of the five cancers. The hypothesis that, because of the difference in distribution of fibrous tremolite, cancer risks in the central area would be greater than in the periphery was thus substantiated. That the explanation may lie in the greater biopersistence of amphibole fibres than chrysotile is important in framing policies for the use and control of asbestos and is directly relevant to the selection of man-made mineral fibre substitutes.

  15. Carcinogenicity and other health effects of acrylonitrile with reference to occupational exposure limit.

    Science.gov (United States)

    Sakurai, H

    2000-04-01

    The occupational exposure limit for acrylonitrile (AN) has been set by many organizations on the basis of its carcinogenicity. However, recent epidemiological studies do not afford evidence supporting the hypothesis that AN is carcinogenic to humans. Review of the 18 published cohort studies revealed that, although there is not adequate evidence in humans for carcinogenicity of AN, the possibility of a causal association between high exposure to AN and lung cancer in humans cannot be excluded. It was pointed out that carcinogenic potential of AN may be weak, if any, to humans, and the current occupational exposure limit (OEL) for AN of 2 ppm was evaluated as appropriate in view of AN exposure levels reported by epidemiological studies. Based also on review of the literature on health effects other than carcinogenicity, it was concluded that the current OEL for AN is a reasonable value and there is no need for a revision at present.

  16. Micropropagation effect on the anti-carcinogenic activitiy of polyphenolics from Mexican oregano (Poliomintha glabrescens Gray) in human colon cancer cells HT-29.

    Science.gov (United States)

    García-Pérez, Enrique; Noratto, Giuliana D; García-Lara, Silverio; Gutiérrez-Uribe, Janet A; Mertens-Talcott, Susanne U

    2013-06-01

    Phenolic extracts obtained from spices are known to have anti-carcinogenic activities but little is known about the effect of micropropagation on these beneficial effects. The main objective of this study was to evaluate the cytotoxic activity of flavonoid-enriched extracts (FEE) from the leaves of wild (WT), in vitro (IN), and ex vitro (EX) grown oregano plants in colon cancer cells HT-29 and the non-cancer cells CCD-18Co. Cell proliferation of HT-29 cells was reduced to 50 % by WT, IN, and EX at concentrations of 4.01, 1.32, and 4.84 mg of gallic acid equivalents (GAE)/L, respectively. In contrast, in CCD-18Co cells, higher concentrations were required for the same cytotoxic effect. At 6 mg GAE/L, WT and IN reduced the production of reactive oxygen species (ROS) of lipopolysaccharides (LPS)-stimulated control cells to 59.89 and 59.43 %, respectively, and EX to 73.89 %. The mRNA of Caspase-3 was increased 1.53-fold when cells were treated with 4 mg GAE/L of IN extract, and tumor necrosis factor receptor superfamily, member 6 (FAS), and BCL2-associated X protein (BAX) mRNA increased 2.55 and 1.53 fold, respectively. Results on protein expression corroborated the apoptotic effects with a significant decrease of B-cell lymphoma 2 (BCL2) expression for all treatments but more remarkable for EX that also showed the most intense signal of BAX. Overall, FEE extracts derived from micropropagation had increased pro-apoptotic effects, however extracts from the in vitro plants produced more efficacy at the transcriptional level while extracts from the ex vitro plant were superior at the traductional level.

  17. A probabilistic modeling approach to assess human inhalation exposure risks to airborne aflatoxin B 1 (AFB 1)

    Science.gov (United States)

    Liao, Chung-Min; Chen, Szu-Chieh

    To assess how the human lung exposure to airborne aflatoxin B 1 (AFB 1) during on-farm activities including swine feeding, storage bin cleaning, corn harvest, and grain elevator loading/unloading, we present a probabilistic risk model, appraised with empirical data. The model integrates probabilistic exposure profiles from a compartmental lung model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing AFB 1 cytotoxicity for inhibition response in human bronchial epithelial cells, to quantitatively estimate the inhalation exposure risks. The risk assessment results implicate that exposure to airborne AFB 1 may pose no significance to corn harvest and grain elevator loading/unloading activities, yet a relatively high risk for swine feeding and storage bin cleaning. Applying a joint probability function method based on exceedence profiles, we estimate that a potential high risk for the bronchial region (inhibition=56.69% with 95% confidence interval (CI): 35.05-72.87%) and bronchiolar region (inhibition=44.93% with 95% CI: 21.61 - 66.78%) is alarming during swine feeding activity. We parameterized the proposed predictive model that should encourage a risk-management framework for discussion of carcinogenic risk in occupational settings where inhalation of AFB 1-contaminated dust occurs.

  18. Development of a Medium-term Animal Model Using gpt Delta Rats to Evaluate Chemical Carcinogenicity and Genotoxicity

    Science.gov (United States)

    Matsushita, Kohei; Kijima, Aki; Ishii, Yuji; Takasu, Shinji; Jin, Meilan; Kuroda, Ken; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    In this study, the potential for development of an animal model (GPG46) capable of rapidly detecting chemical carcinogenicity and the underlying mechanisms of action were examined in gpt delta rats using a reporter gene assay to detect mutations and a medium-term rat liver bioassay to detect tumor promotion. The tentative protocol for the GPG46 model was developed based on the results of dose-response exposure to diethylnitrosamine (DEN) and treatment with phenobarbital over time following DEN administration. Briefly, gpt delta rats were exposed to various chemicals for 4 weeks, followed by a partial hepatectomy (PH) to collect samples for an in vivo mutation assay. The mutant frequencies (MFs) of the reporter genes were examined as an indication of tumor initiation. A single intraperitoneal (ip) injection of 10 mg/kg DEN was administered to rats 18 h after the PH to initiate hepatocytes. Tumor-promoting activity was evaluated based on the development of glutathione S-transferase placental form (GST-P)-positive foci at week 10. The genotoxic carcinogens 2-acetylaminofluorene (2-AAF), 2-amino-3-methylimidazo [4,5-f] quinolone (IQ) and safrole (SF), the non-genotoxic carcinogens piperonyl butoxide (PBO) and phenytoin (PHE), the non-carcinogen acetaminophen (APAP) and the genotoxic non-hepatocarcinogen aristolochic acid (AA) were tested to validate the GPG46 model. The validation results indicate that the GPG46 model could be a powerful tool in understanding chemical carcinogenesis and provide valuable information regarding human risk hazards. PMID:23723564

  19. Oxidative Stress Mechanisms Do Not Discriminate between Genotoxic and Nongenotoxic Liver Carcinogens.

    Science.gov (United States)

    Deferme, Lize; Wolters, Jarno; Claessen, Sandra; Briedé, Jacco; Kleinjans, Jos

    2015-08-17

    It is widely accepted that in chemical carcinogenesis different modes-of-action exist, e.g., genotoxic (GTX) versus nongenotoxic (NGTX) carcinogenesis. In this context, it has been suggested that oxidative stress response pathways are typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress-related changes in gene expression, cell cycle distribution, and (oxidative) DNA damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX-, and noncarcinogens, at multiple time points (4-8-24-48-72 h). Two GTX (azathriopine (AZA) and furan) and two NGTX (tetradecanoyl-phorbol-acetate, (TPA) and tetrachloroethylene (TCE)) carcinogens as well as two noncarcinogens (diazinon (DZN, d-mannitol (Dman)) were selected, while per class one compound was deemed to induce oxidative stress and the other not. Oxidative stressors AZA, TPA, and DZN induced a 10-fold higher number of gene expression changes over time compared to those of furan, TCE, or Dman treatment. Genes commonly expressed among AZA, TPA, and DZN were specifically involved in oxidative stress, DNA damage, and immune responses. However, differences in gene expression between GTX and NGTX carcinogens did not correlate to oxidative stress or DNA damage but could instead be assigned to compound-specific characteristics. This conclusion was underlined by results from functional readouts on ROS formation and (oxidative) DNA damage. Therefore, oxidative stress may represent the underlying cause for increased risk of liver toxicity and even carcinogenesis; however, it does not discriminate between GTX and NGTX carcinogens.

  20. 78 FR 15020 - Report on Carcinogens Webinar on Pentachlorophenol; Notice of Public Webinar and Registration...

    Science.gov (United States)

    2013-03-08

    ... HUMAN SERVICES National Institutes of Health Report on Carcinogens Webinar on Pentachlorophenol; Notice of Public Webinar and Registration Information SUMMARY: The National Toxicology Program (NTP) announces a public webinar, ``Human cancer studies on exposure to pentachlorophenol (PCP):...

  1. Dietary acrylamide intake is not associated with gastrointestinal cancer risk

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Acrylamide is a probable human carcinogen that was detected in several heat-treated foods, such as French fries and crisps, in 2002. Prospective studies are needed on acrylamide and human cancer risk. We prospectively investigated the association between acrylamide and gastrointestinal cancer risk.

  2. Dietary acrylamide intake is not associated with gastrointestinal cancer risk

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Acrylamide is a probable human carcinogen that was detected in several heat-treated foods, such as French fries and crisps, in 2002. Prospective studies are needed on acrylamide and human cancer risk. We prospectively investigated the association between acrylamide and gastrointestinal cancer risk.

  3. Anal human papillomavirus in HIV-uninfected men who have sex with men: incidence and clearance rates, duration of infection, and risk factors.

    Science.gov (United States)

    Donà, M G; Vescio, M F; Latini, A; Giglio, A; Moretto, D; Frasca, M; Benevolo, M; Rollo, F; Colafigli, M; Cristaudo, A; Giuliani, M

    2016-12-01

    Little is known regarding the natural history of anal human papillomavirus (HPV) infection. We aimed to evaluate incidence and clearance rates, their risk factors, and duration of anal HPV infection in HIV-uninfected men who have sex with men (MSM). A longitudinal study was conducted. Anal samples were analysed using the Linear Array HPV Genotyping test. Incidence and clearance rates, and corresponding risk factors, were estimated using a two-state Markov model. Overall, 155 MSM (median age 33.4 years) attending the largest sexually transmitted infection (STI) centre in Rome, Italy, were followed for a median of 12.2 months (Q1-Q3: 7.0-18.1). Incidence and clearance rates for any HPV were 85.6 (95% CI: 58.4-125.4) and 35.6 (95% CI: 24.7-51.5) × 1000 person-months, respectively; the median duration of infection was 9.4 months (Q1-Q3: 7.5-12.1). Receptive anal sex emerged as the only risk factor for the acquisition of any HPV (Hazard Ratio, HR = 2.65, 95% CI: 1.16-6.06). The incidence rates for carcinogenic and non-carcinogenic types were 42.3 (95% CI: 29.2-61.4) and 29.2 (95% CI: 19.5-43.7) × 1000 person-months, respectively (p = 0.13); their clearance rates were 62.9 (95% CI: 45.1-87.7) and 65.7 (95% CI: 47.4-91.0) × 1000 person-months, respectively (p = 0.83). HPV16 showed the lowest clearance rate among carcinogenic types (59.7 × 1000 person-months), and a duration of infection of 16.8 months. In conclusion, a higher incidence rate was observed for carcinogenic compared to non-carcinogenic HPV types, although the difference was not significant. HPV16 emerged as the type with the longest duration of infection and the lowest clearance rate among carcinogenic types.

  4. Occurrence, uses, and carcinogenicity of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2015-01-01

    Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

  5. Main components and human health risks assessment of PM10, PM2.5, and PM1 in two areas influenced by cement plants

    Science.gov (United States)

    Sánchez-Soberón, Francisco; Rovira, Joaquim; Mari, Montse; Sierra, Jordi; Nadal, Martí; Domingo, José L.; Schuhmacher, Marta

    2015-11-01

    Particulate matter (PM) is widely recorded as a source of diseases, being more harmful those particles with smaller size. PM is released to the environment as a consequence of different activities, being one of them cement production. The objective of this pilot study was to characterize PM of different sizes around cement facilities to have a preliminary approach of their origin, and evaluate their potential health risks. For that purpose, three fractions of PM (10, 2.5, and 1) were collected in the nearby area of two cement plants with different backgrounds (urban and rural) in different seasons. Subsequently, main components, outdoor and indoor concentrations, exposure, and human health risks were assessed. Greatest levels of PM1, organic matter, and metals were found in urban location, especially in winter. Consequently, environmental exposure and human health risks registered their highest values in the urban plant during wintertime. Exposure was higher for indoor activities, expressing some metals their peak values in the PM1 fraction. Non-carcinogenic risks were below the safety threshold (HQ < 1). Carcinogenic risks for most of the metals were below the limit of 10-5, except for Cr (VI), which exceeded it in both locations, but being in the range considered as assumable (10-6-10-4).

  6. The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution: focus on China.

    Science.gov (United States)

    Loomis, Dana; Huang, Wei; Chen, Guosheng

    2014-04-01

    The International Agency for Research on Cancer (IARC) has classified outdoor air pollution and the particulate matter (PM) in outdoor air pollution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pollution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pollution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pollutants. Excess cancer risk is also observed in experimental animals exposed to polluted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pollution in China and the urgent need to act to reduce exposure to the population.

  7. The International Agency for Research on Cancer (IARC) evaluation of the carcinogenicity of outdoor air pollution:focus on China

    Institute of Scientific and Technical Information of China (English)

    Dana Loomis; Wei Huang; Guosheng Chen

    2014-01-01

    The International Agency for Research on Cancer (IARC) has classified outdoor air pol ution and the particulate matter (PM) in outdoor air pol ution as carcinogenic to humans, as based on sufficient evidence of carcinogenicity in humans and experimental animals and strong support by mechanistic studies. The data with important contributions to the evaluation are reviewed, highlighting the data with particular relevance to China, and implications of the evaluation with respect to China are discussed. The air pol ution levels in Chinese cities are among the highest observed in the world today and frequently exceed health-based national and international guidelines. Data from high-quality epidemiologic studies in Asia, Europe, and North America consistently show positive associations between lung cancer and PM exposure and other indicators of air pol ution, which persist after adjustment for important lung cancer risk factors, such as tobacco smoking. Epidemiologic data from China are limited but nevertheless indicate an increased risk of lung cancer associated with several air pol utants. Excess cancer risk is also observed in experimental animals exposed to pol uted outdoor air or extracted PM. The exposure of several species to outdoor air pollution is associated with markers of genetic damage that have been linked to increased cancer risk in humans. Numerous studies from China, especially genetic biomarker studies in exposed populations, support that the polluted air in China is genotoxic and carcinogenic to humans. The evaluation by IARC indicates both the need for further research into the cancer risks associated with exposure to air pol ution in China and the urgent need to act to reduce exposure to the population.

  8. The carcinogenicity of dietary acrylamide intake: A comparative discussion of epidemiological and experimental animal research

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Baars, B.-J.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2010-01-01

    Since 2002, it is known that the probable human carcinogen acrylamide is present in commonly consumed carbohydrate-rich foods, such as French fries and potato chips. In this review, the authors discuss the body of evidence on acrylamide carcinogenicity from both epidemiological and rodent studies, i

  9. 78 FR 4419 - Draft Report on Carcinogens Monographs for 1-Bromopropane and Cumene; Availability of Documents...

    Science.gov (United States)

    2013-01-22

    ... HUMAN SERVICES National Institutes of Health Draft Report on Carcinogens Monographs for 1-Bromopropane... meeting of the Draft Report on Carcinogens (RoC) Monographs for 1-Bromopropane and Cumene. These documents....m. until adjournment, approximately 2:00 p.m. EDT. Document Availability: Draft monographs will...

  10. [Prediction of PCBs uptake by vegetable in a representative area and evaluation of the human health risk by Trapp model].

    Science.gov (United States)

    Deng, Shao-Po; Luo, Yong-Ming; Song, Jing; Teng, Ying; Chen, Yong-Shan

    2010-12-01

    Air, soil and vegetable samples were collected from an e-waste disassembly site and analyzed for characteristic contaminants PCBs. Based on the measured PCBs concentrations in soil and air, PCBs concentration in leafy vegetables was predicted by Trapp Model and the sources, composition of PCBs in vegetable and influencing factors were analyzed. By using human health risk assessment model of USEPA, risk to human health from consumption of vegetable that take up PCBs from environment was evaluated. The results showed that the Trapp Model could give good prediction of PCBs concentrations in leafy vegetables based on PCBs concentration in the soil and air. For instance, the measured sum of seven PCBs in vegetable was 51.2 microg x kg(-1) and the predicted value was 39.9 microg x kg(-1). So the predicted value agrees well with the measured value. The gaseous PCBs were the main source of PCBs in leafy vegetables, and the model predicting results indicated that the contribution rate was as high as 98.8%. The uptake pathway, n-octanol/water partition coefficient (K(ow)) and the n-octanol/air partition coefficient (K(oa)) of PCBs determine the concentration and composition of PCBs in vegetables. The duration needed for PCBs uptake to reach equilibrium was in good correlation with lgK(ow) and lgK(oa). Multiple linear regression analysis indicated that lgK(oa) was more important. Carcinogenic risk from consumption of PCBs contaminated vegetables was 10 000 times higher than that of gaseous PCBs, and the no-carcinogenic risk was increased by approximately 200 times. The main reasons are firstly the vegetables take up and accumulate more toxic PCBs with high-chloride substitutes and consequently the oral toxic factors of PCBs increase dramatically. Secondly, an adult takes 71 times more PCBs via consumption of vegetables than via inhalation of air.

  11. Assessment of ecological and human health risks of heavy metal contamination in agriculture soils disturbed by pipeline construction.

    Science.gov (United States)

    Shi, Peng; Xiao, Jun; Wang, Yafeng; Chen, Liding

    2014-02-28

    The construction of large-scale infrastructures such as nature gas/oil pipelines involves extensive disturbance to regional ecosystems. Few studies have documented the soil degradation and heavy metal contamination caused by pipeline construction. In this study, chromium (Cr), cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) levels were evaluated using Index of Geo-accumulation (Igeo) and Potential Ecological Risk Index (RI) values, and human health risk assessments were used to elucidate the level and spatial variation of heavy metal pollution risks. The results showed that the impact zone of pipeline installation on soil heavy metal contamination was restricted to pipeline right-of-way (RoW), which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50 m. RI showed a declining tendency in different zones as follows: trench > working zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health risks than that of 20 m and 50 m, and children were more susceptible to non-carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had similar sources, drawing attention to the anthropogenic activity. The findings in this study should help better understand the type, degree, scope and sources of heavy metal pollution from pipeline construction to reduce pollutant emissions, and are helpful in providing a scientific basis for future risk management.

  12. Assessment of Ecological and Human Health Risks of Heavy Metal Contamination in Agriculture Soils Disturbed by Pipeline Construction

    Directory of Open Access Journals (Sweden)

    Peng Shi

    2014-02-01

    Full Text Available The construction of large-scale infrastructures such as nature gas/oil pipelines involves extensive disturbance to regional ecosystems. Few studies have documented the soil degradation and heavy metal contamination caused by pipeline construction. In this study, chromium (Cr, cadmium (Cd, copper (Cu, nickel (Ni, lead (Pb and zinc (Zn levels were evaluated using Index of Geo-accumulation (Igeo and Potential Ecological Risk Index (RI values, and human health risk assessments were used to elucidate the level and spatial variation of heavy metal pollution risks. The results showed that the impact zone of pipeline installation on soil heavy metal contamination was restricted to pipeline right-of-way (RoW, which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50 m. RI showed a declining tendency in different zones as follows: trench > working zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health risks than that of 20 m and 50 m, and children were more susceptible to non-carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had similar sources, drawing attention to the anthropogenic activity. The findings in this study should help better understand the type, degree, scope and sources of heavy metal pollution from pipeline construction to reduce pollutant emissions, and are helpful in providing a scientific basis for future risk management.

  13. Assessment of Ecological and Human Health Risks of Heavy Metal Contamination in Agriculture Soils Disturbed by Pipeline Construction

    Science.gov (United States)

    Shi, Peng; Xiao, Jun; Wang, Yafeng; Chen, Liding

    2014-01-01

    The construction of large-scale infrastructures such as nature gas/oil pipelines involves extensive disturbance to regional ecosystems. Few studies have documented the soil degradation and heavy metal contamination caused by pipeline construction. In this study, chromium (Cr), cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) levels were evaluated using Index of Geo-accumulation (Igeo) and Potential Ecological Risk Index (RI) values, and human health risk assessments were used to elucidate the level and spatial variation of heavy metal pollution risks. The results showed that the impact zone of pipeline installation on soil heavy metal contamination was restricted to pipeline right-of-way (RoW), which had higher Igeo of Cd, Cu, Ni and Pb than that of 20 m and 50 m. RI showed a declining tendency in different zones as follows: trench > working zone > piling area > 20 m > 50 m. Pipeline RoW resulted in higher human health risks than that of 20 m and 50 m, and children were more susceptible to non-carcinogenic hazard risk. Cluster analysis showed that Cu, Ni, Pb and Cd had similar sources, drawing attention to the anthropogenic activity. The findings in this study should help better understand the type, degree, scope and sources of heavy metal pollution from pipeline construction to reduce pollutant emissions, and are helpful in providing a scientific basis for future risk management. PMID:24590049

  14. A proposed unified mechanism for the reduction of human breast cancer risk by the hormones of pregnancy.

    Science.gov (United States)

    Jacobson, Herbert I; Lemanski, Nicole; Agarwal, Anu; Narendran, Amithi; Turner, Kelvin E; Bennett, James A; Andersen, Thomas T

    2010-02-01

    Parity in women is associated with reduced lifetime risk of breast cancer, and hormones of pregnancy [estrogen (E), progesterone (P), human chorionic gonadotropin (hCG)] are implicated. Parity also reduces mammary cancer risk in carcinogen-exposed rats, and administering pregnancy hormones to these animals is similarly effective. Because pregnancy hormones are also able to stimulate cancer growth, we proposed to resolve this dichotomy by determining whether administered pregnancy hormones elicit the cancer-inhibiting agent alpha-fetoprotein (AFP) from the liver, which would implicate AFP as a proximal effector of hormonal anticancer activity. Accordingly, we treated groups of nitrosomethylurea-exposed rats with saline, E(3), E(2) + P, E(3) + P, hCG, or allowed them to experience pregnancy, and then monitored mammary cancer incidence and serum levels of AFP over time. Each hormone treatment reduced mammary cancer incidence and elevated serum AFP levels. To challenge human tissues, human HepG2 liver cells in culture were treated with the same hormonal agents. Each hormone regimen increased the levels of AFP in the culture medium. Medium containing AFP elicited by hCG inhibited the E(2)-stimulated proliferation of cultured human MCF7 breast cancer cells, whereas hCG alone did not inhibit their growth. Furthermore, antibodies to AFP neutralized the growth-inhibiting effect of AFP-containing HepG2 medium. We conclude that in the treatment of carcinogen-exposed rats with the hormones of pregnancy, and by inference in women who have experienced pregnancy, that AFP is a proximal agent that inhibits mammary gland cancer.

  15. Trichloroethylene risk assessment: relevance of interindividual differences

    NARCIS (Netherlands)

    Vermeulen, N.P.E.; Bladeren, P.J. van

    2001-01-01

    Interindividual variability in the disposition and effects of xenobiotics in humans and related inter-species differences should play a major role in human risk assessment. In particular for low-dose exposures to potentially carcinogenic compounds, novel tools and concepts are necessary to assess

  16. Trichloroethylene risk assessment: relevance of interindividual differences

    NARCIS (Netherlands)

    Vermeulen, N.P.E.; Bladeren, P.J. van

    2001-01-01

    Interindividual variability in the disposition and effects of xenobiotics in humans and related inter-species differences should play a major role in human risk assessment. In particular for low-dose exposures to potentially carcinogenic compounds, novel tools and concepts are necessary to assess ri

  17. A dynamic human health risk assessment system.

    Science.gov (United States)

    Prasad, Umesh; Singh, Gurmit; Pant, A B

    2012-05-01

    An online human health risk assessment system (OHHRAS) has been designed and developed in the form of a prototype database-driven system and made available for the population of India through a website - www.healthriskindia.in. OHHRAS provide the three utilities, that is, health survey, health status, and bio-calculators. The first utility health survey is functional on the basis of database being developed dynamically and gives the desired output to the user on the basis of input criteria entered into the system; the second utility health status is providing the output on the basis of dynamic questionnaire and ticked (selected) answers and generates the health status reports based on multiple matches set as per advise of medical experts and the third utility bio-calculators are very useful for the scientists/researchers as online statistical analysis tool that gives more accuracy and save the time of user. The whole system and database-driven website has been designed and developed by using the software (mainly are PHP, My-SQL, Deamweaver, C++ etc.) and made available publically through a database-driven website (www.healthriskindia.in), which are very useful for researchers, academia, students, and general masses of all sectors.

  18. 10. NON-CANCER DATA IN THE EVALUATION OF HUMAN CANCER RISK FROM SPECIFIC CHEMICALS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Exposure levels, noncancer effects and susceptibility factors can all be assessed in humans exposed to environmental carcinogens. Added to the vast armamentarium of traditional biomarkers currently available for these purposes are novel ones constantly emerging from the rapidly developing areas of toxicogenomics and proteomics.

  19. Chlorophenols in marine organisms from the southern coast of Hangzhou Bay, China, and an assessment of risks posed to human health

    Science.gov (United States)

    Zheng, Dan; Jiao, Haifeng; Zhong, Huiying; Qiu, Jishi; Yan, Xiaojun; Duan, Qingyuan; Chai, Liyue

    2017-06-01

    The composition of chlorophenols in marine organisms from the southern coast of Hangzhou Bay, China, was analyzed and the health risks posed to humans assessed. A total of 19 chlorophenols from 16 types of marine organism were analyzed across nine survey sections in Hangzhou Bay. The chlorophenols were analyzed by gas chromatography-mass spectrometry using a DB-5MS quartz capillary column. The concentrations of monochlorophenol, dichlorophenol, trichlorophenol, tetrachlorophenol, and pentachlorophenol ranged from below the detection limit (ND) to 132 μg/kg, ND-51.0 μg/kg, ND-42.5 μg/kg, ND-69.0 μg/kg, and ND-9.06 μg/kg, respectively. Additionally, concentration differences between each type of chlorophenol were not signifi cant (P>0.05). However, signifi cant differences were found between monochlorophenol (F=8.13, Prisk indices were risk was posed by 2-chlorophenol, 2,4-dichlorophenol, 2,4,6-trichlorophenol, 2,4,5-trichlorophenol, 2,3,4,6-tetrachlorophenol, and pentachlorophenol to humans consuming marine organisms from the study area. Furthermore, the carcinogenic risks posed by 2,4,6-trichlorophenol and pentachlorophenol were lower than limits set by the International Commission on Radiological Protection and the US Environmental Protection Agency. However, the noncarcinogenic and carcinogenic risks posed by chlorophenols in marine organisms from four of the survey sections (Sizaopu, Niluoshan, Longshan Town and Xinhong zha) were higher than the other survey sections.

  20. Human health risk assessment, congener specific analysis and spatial distribution pattern of organochlorine pesticides (OCPs) through rice crop from selected districts of Punjab Province, Pakistan.

    Science.gov (United States)

    Mumtaz, Mehvish; Qadir, Abdul; Mahmood, Adeel; Mehmood, Andleeb; Malik, Riffat Naseem; Li, Jun; Yousaf, Zubaida; Jamil, Nadia; Shaikh, Irfan Ahmed; Ali, Habib; Zhang, Gan

    2015-04-01

    To evaluate the screening level risk assessment of OCPs in rice (Oryza sativa L.) straw (n=20) and rice grains (n=20), samples were collected from different districts of Punjab Province, Pakistan. ∑OCPs' levels (ng g(-1)) in rice straw and grains ranged from 3.63 to 39.40, 2.72 to 49.89, respectively. DDTs were found predominant over the other detected OCP isomers followed by HCH and heptachlor. Results of one way ANOVA reflected no significant difference for OCPs' levels among sampling sites, except heptachlor for rice grains. ∑OCPs' concentration in rice straw samples was exceeding the minimal residual levels (MRLs) (Australian and Japanese). Results of dietary intake and risk assessment suggested that rice straw is not safe for animals to consume as fodder. Human health was suggested to have some carcinogenic risks by consumption of rice grains, however, no considerable hazardous risk (non-carcinogenic) to human health was found. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Life cycle and human health risk assessments as tools for decision making in the design and implementation of nanofiltration in drinking water treatment plants.

    Science.gov (United States)

    Ribera, G; Clarens, F; Martínez-Lladó, X; Jubany, I; V Martí; Rovira, M

    2014-01-01

    A combined methodology using life cycle assessment (LCA) and human health risk assessment (HHR) is proposed in order to select the percentage of water in drinking water treatment plants (DWTP) that should be nanofiltered (NF). The methodological approach presented here takes into account environmental and social benefit criteria evaluating the implementation of new processes into conventional ones. The inclusion of NF process improves drinking water quality, reduces HHR but, in turn, increases environmental impacts as a result of energy and material demand. Results from this study lead to balance the increase of the impact in various environmental categories with the reduction in human health risk as a consequence of the respective drinking water production and consumption. From an environmental point of view, the inclusion of NF and recommended pretreatments to produce 43% of the final drinking water means that the environmental impact is nearly doubled in comparison with conventional plant in impact categories severely related with electricity production, like climate change. On the other hand, the carcinogenic risk (HHR) associated to trihalomethane formation potential (THMFP) decreases with the increase in NF percentage use. Results show a reduction of one order of magnitude for the carcinogenic risk index when 100% of drinking water is produced by NF.

  2. International Conference on Harmonisation: guidance on testing for carcinogenicity of pharmaceuticals. Notice. Food and Drug Administration, HHS.

    Science.gov (United States)

    1998-02-23

    The Food and Drug Administration (FDA) is publishing a guidance entitled "S1B Testing for Carcinogenicity of Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance outlines experimental approaches to evaluating the carcinogenic potential of pharmaceuticals to humans that may obviate the necessity for the routine conduct of two long-term rodent carcinogenicity studies

  3. Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

    Science.gov (United States)

    Labib, Sarah; Bourdon-Lacombe, Julie; Kuo, Byron; Buick, Julie K.; Lemieux, France; Williams, Andrew; Halappanavar, Sabina; Malik, Amal; Luijten, Mirjam; Aubrecht, Jiri; Hyduke, Daniel R.; Fornace, Albert J.; Swartz, Carol D.; Recio, Leslie; Yauk, Carole L.

    2015-01-01

    Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work. PMID:25605026

  4. Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

    Science.gov (United States)

    Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

    2004-01-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

  5. Predicting Risk Sensitivity in Humans and Lower Animals: Risk as Variance or Coefficient of Variation

    Science.gov (United States)

    Weber, Elke U.; Shafir, Sharoni; Blais, Ann-Renee

    2004-01-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk…

  6. Human health risk assessment of dissolved metals in groundwater and surface waters in the Melen watershed, Turkey.

    Science.gov (United States)

    Çelebi, Ahmet; Sengörür, Bülent; Kløve, Bjørn

    2014-01-01

    Determination of metal risk levels in potable water and their effects on human health are vital in assessment of water resources. Risk assessment of metals to human health in a watershed, which has not been studied before, is the main objective of the present study. Surface and groundwater sampling was carried out between September 2010 and August 2011 in the Melen Watershed, Turkey, an important drinking water resource for millions of people. Metals were analyzed in the laboratory using inductively coupled plasma. Of the 26 different metals monitored, Al, B, Ba, Cr, Cu, Fe, Mn, Mo and V were found in surface water and As, B, Ba, Cr, Cu, Mn, Mo, V and Zn in groundwater. In groundwater, unitless hazard quotient (HQ) values were 6 for As, 2.7 for Mn and 1 for Zn, while in surface water all metals were below the risk level (HQ watersheds can pose a risk to human health and that potential carcinogenic impacts should receive more attention.

  7. Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms.

    Science.gov (United States)

    Ge, Guang-Zhe; Xu, Tian-Rui; Chen, Ceshi

    2015-07-01

    Tobacco usage is a major risk factor in the development, progression, and outcomes for lung cancer. Of the carcinogens associated with lung cancer, tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is among the most potent ones. The oncogenic mechanisms of NNK are not entirely understood, hindering the development of effective strategies for preventing and treating smoking-associated lung cancers. Here, we introduce the NNK-induced lung cancer animal models in different species and its potential mechanisms. Finally, we summarize several chemopreventive agents developed from these animal models.

  8. GENETIC POLYMORPHISMS IN HUMAN LIVER PHENOL SULFOTRANSFERASES INVOLVED IN THE BIOACTIVATION OF N-HYDROXY DERIVATIVES OF CARCINOGENIC ARYLAMINES AND HETEROCYCLIC AMINES. (R825280)

    Science.gov (United States)

    AbstractThree related forms of phenol sulfotransferase (PSULT), thermostable ST1A2 (SULT1A2hum) and ST1A3 (SULT1A1hum) and a thermolabile TL-PST (SULT1A3hum), are known to exist in human livers. Thermostable forms, whose activities are polymorphically distributed, hav...

  9. Statement on the risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements

    DEFF Research Database (Denmark)

    Petersen, Annette

    that there was a possible health concern for those toddlers and children who are high consumers of honey. A new exposure assessment including new occurrence data was published by EFSA in 2016 and was used to update the risk characterisation. The CONTAM Panel established a new Reference Point of 237 μg/kg body weight per......EFSA was asked by the European Commission to deliver a scientific opinion on the risks for human health related to the presence of pyrrolizidine alkaloids (PAs) in honey, tea, herbal infusions and food supplements and to identify the PAs of relevance in the aforementioned food commodities...... day to assess the carcinogenic risks of PAs, and concluded that there is a possible concern for human health related to the exposure to PAs, in particular for frequent and high consumers of tea and herbal infusions. The Panel noted that consumption of food supplements based on PA-producing plants...

  10. Risk of human exposure to polycyclic aromatic hydrocarbons: A case study in Beijing, China.

    Science.gov (United States)

    Yu, Yanxin; Li, Qi; Wang, Hui; Wang, Bin; Wang, Xilong; Ren, Aiguo; Tao, Shu

    2015-10-01

    Polycyclic aromatic hydrocarbons (PAHs) can cause adverse effects on human health. The relative contributions of their two major intake routes (diet and inhalation) to population PAH exposure are still unclear. We modeled the contributions of diet and inhalation to the overall PAH exposure of the population of Beijing in China, and assessed their human incremental lifetime cancer risks (ILCR) using a Mont Carlo simulation approach. The results showed that diet accounted for about 85% of low-molecular-weight PAH (L-PAH) exposure, while inhalation accounted for approximately 57% of high-molecular-weight PAH (H-PAH) exposure of the Beijing population. Meat and cereals were the main contributors to dietary PAH exposure. Both gaseous- and particulate-phase PAHs contributed to L-PAH exposure through inhalation, whereas exposure to H-PAHs was mostly from the particulate-phase. To reduce the cancer incidence of the Beijing population, more attention should be given to inhaled particulate-phase PAHs with considerable carcinogenic potential.

  11. Risk Assessment: Perchloroethylene Dry Cleaners Refined Human Health Risk Characterization

    Science.gov (United States)

    This November 2005 memo and appendices describe the methods by which EPA conducted its refined risk assessment of the Major Source and Area Source facilities within the perchloroethylene (perc) dry cleaners source category.

  12. Human Health and Ecological Risk Assessment of 16 Polycyclic Aromatic Hydrocarbons in Drinking Source Water from a Large Mixed-Use Reservoir.

    Science.gov (United States)

    Sun, Caiyun; Zhang, Jiquan; Ma, Qiyun; Chen, Yanan

    2015-10-30

    Reservoirs play an important role in living water supply and irrigation of farmlands, thus the water quality is closely related to public health. However, studies regarding human health and ecological risk assessment of polycyclic aromatic hydrocarbons (PAHs) in the waters of reservoirs are very few. In this study, Shitou Koumen Reservoir which supplies drinking water to 8 million people was investigated. Sixteen priority PAHs were analyzed in a total of 12 water samples. In terms of the individual PAHs, the average concentration of Fla, which was 5.66 × 10(-1) μg/L, was the highest, while dibenz(a,h)anthracene which was undetected in any of the water samples was the lowest. Among three PAH compositional patterns, the concentration of low-molecular-weight and 4-ring PAHs was dominant, accounting for 94%, and the concentration of the total of 16 PAHs was elevated in constructed-wetland and fish-farming areas. According to the calculated risk quotients, little or no adverse effects were posed by individual and complex PAHs in the water on the aquatic ecosystem. In addition, the results of hazard quotients for non-carcinogenic risk also showed little or no negative impacts on the health of local residents. However, it could be concluded from the carcinogenic risk results that chrysene and complex PAHs in water might pose a potential carcinogenic risk to local residents. Moreover, the possible sources of PAHs were identified as oil spills and vehicular emissions, as well as the burning of biomass and coal.

  13. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I

    Energy Technology Data Exchange (ETDEWEB)

    Levova, Katerina; Moserova, Michaela [Department of Biochemistry, Faculty of Science, Charles University, Prague (Czech Republic); Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati (United States); Phillips, David H. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London (United Kingdom); Frei, Eva [Division of Preventive Oncology, National Center for Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schmeiser, Heinz H. [Research Group Genetic Alterations in Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg (Germany); Arlt, Volker M. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London (United Kingdom); Stiborova, Marie, E-mail: stiborov@natur.cuni.cz [Department of Biochemistry, Faculty of Science, Charles University, Prague (Czech Republic)

    2012-12-15

    Aristolochic acid causes a specific nephropathy (AAN), Balkan endemic nephropathy, and urothelial malignancies. Using Western blotting suitable to determine protein expression, we investigated in several transgenic mouse lines expression of NAD(P)H:quinone oxidoreductase (NQO1)—the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI). The mouse tissues used were from previous studies [Arlt et al., Chem. Res. Toxicol. 24 (2011) 1710; Stiborova et al., Toxicol. Sci. 125 (2012) 345], in which the role of microsomal cytochrome P450 (CYP) enzymes in AAI metabolism in vivo had been determined. We found that NQO1 levels in liver, kidney and lung of Cyp1a1(−/−), Cyp1a2(−/−) and Cyp1a1/1a2(−/−) knockout mouse lines, as well as in two CYP1A-humanized mouse lines harboring functional human CYP1A1 and CYP1A2 and lacking the mouse Cyp1a1/1a2 orthologs, differed from NQO1 levels in wild-type mice. NQO1 protein and enzymic activity were induced in hepatic and renal cytosolic fractions isolated from AAI-pretreated mice, compared with those in untreated mice. Furthermore, this increase in hepatic NQO1 enzyme activity was associated with bioactivation of AAI and elevated AAI-DNA adduct levels in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, AAI appears to increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential. Highlights: ► NAD(P)H:quinone oxidoreductase expression in Cyp1a knockout and humanized CYP1A mice ► Reductive activation of the nephrotoxic and carcinogenic aristolochic acid I (AAI) ► NAD(P)H:quinone oxidoreductase is induced in mice treated with AAI. ► Induced hepatic enzyme activity resulted in elevated AAI-DNA adduct levels.

  14. Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice

    Energy Technology Data Exchange (ETDEWEB)

    Cornelis, J.J.; Becquart, P.; Duponchel, N.; Salome, N.; Avalosse, B.L.; Namba, M.; Rommelaere, J.

    1988-05-01

    Morphologically altered and established human fibroblasts, obtained either by /sup 60/Co gamma irradiation, treatment with the carcinogen 4-nitroquinoline 1-oxide, or simian virus 40 (SV40) infection, were compared with their normal finite-life parental strains for susceptibility to the autonomous parvoviruses H-1 virus and the prototype strain of minute virus of mice (MVMp). All transformed cells suffered greater virus-induced killing than their untransformed progenitors. The cytotoxic effect of H-1 virus was more severe than that of MVMp. Moreover, the level of viral DNA replication was much (10- to 85-fold) enhanced in the transformants compared with their untransformed parent cells. Thus, in this system, cell transformation appears to correlate with an increase in both DNA amplification and cytotoxicity of the parvoviruses. However, the accumulation of parvovirus DNA in the transformants was not always accompanied by the production of infectious virus. Like in vitro-transformed fibroblasts, a fibrosarcoma-derived cell line was sensitive to the killing effect of both H-1 virus and MVMp and amplified viral DNA to high extents. The results indicate that oncogenic transformation can be included among cellular states which modulate permissiveness to parvoviruses under defined growth conditions.

  15. Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice

    Energy Technology Data Exchange (ETDEWEB)

    Cornelis, J.J.; Becquart, P.; Duponchel, N.; Salome, N.; Avalosse, B.L.; Namba, M.; Rommelaere, J.

    1988-05-01

    Morphologically altered and established human fibroblasts, obtained either by /sup 60/Co gamma irradiation, treatment with the carcinogen 4-nitroquinoline 1-oxide, or simian virus 40 (SV40) infection, were compared with their normal finite-life parental strains for susceptibility to the autonomous parvoviruses H-1 virus and the prototype strain of minute virus of mice (MVMp). All transformed cells suffered greater virus-induced killing than their untransformed progenitors. The cytotoxic effect of H-1 virus was more severe than that of MVMp. Moreover, the level of viral DNA replication was much (10- to 85-fold) enhanced in the transformants compared with their untransformed parent cells. Thus, in this system, cell transformation appears to correlate with an increase in both DNA amplification and cytotoxicity of the parvoviruses. However, the accumulation of parvovirus DNA in the transformants was not always accompanied by the production of infectious virus. Like in vitro-transformed fibroblasts, a fibrosarcoma-derived cell line was sensitive to the killing effect of both H-1 virus and MVMp and amplified viral DNA to high extents. The results indicate that oncogenic transformation can be included among cellular states which modulate permissiveness to parvoviruses under defined growth conditions.

  16. [Carcinogenic risks associated with radiation pollution].

    Science.gov (United States)

    Latarjet, R

    1976-01-01

    1. The cancerogenic pollution by non-ionizing radiations is limited to the case of solar ultraviolet, whose activity at ground level may be increased as a consequence of the stratospheric depletion of ozone, itself produced by certain chemical pollutants: nitrogen oxydes from supersonic aircrafts, freon. 2. As regards ionizing radiations, the discussion is focused on the fundamental problem of the "threshold", aand on the means by which one may obtain some quantitative data related to carcinogenesis by small radiation doses in Man. A new concept, that of a "practical threshold" is proposed. 3. One discusses a theory which links radiocancerogenesis, as well as chemical cancerogenesis, to errors produced in the repair of lesions in the DNA. 4. One presents and discusses the "rads-equivalent" project for chemical mutagens and cancerogens.

  17. A call to expand regulation to all carcinogenic fibrous minerals

    Science.gov (United States)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    vitro and in vivo studies have shown its toxic and carcinogenic properties; 2) the carcinogenic properties of erionite have been demonstrated, and erionite has been associated with a mesothelioma epidemic in Anatolia, Turkey. Erionite is also widespread in areas of north central USA, where it is contained in gravel paving stone, and is cause for concern due to increased commercial traffic. Numerous studies have shown that non-regulated fibrous materials pose similar health hazards to regulated "asbestos". An increase in human activities in areas where these fibrous minerals are present, such as in surficial rock and soil, will result in the generation of airborne dust, exposing people to carcinogenic fibers. The current limited regulation leads people to believe that only the six mineral fibers referred to as "asbestos" are dangerous. We propose that fibrous minerals should be regulated as a single group, as they have similar deleterious effects on the human body. Regulations would be simplified and more effective if they embrace all carcinogenic fibrous minerals.

  18. Impact of Environmental Exposures on the Mutagenicity/Carcinogenicity of Heterocyclic Amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Knize, M G; Bennett, L M; Malfatti, M A; Colvin, M E; Kulp, K S

    2003-12-19

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.

  19. Risk perception, risk evaluation and human values: cognitive bases of acceptability of a radioactive waste repository

    Energy Technology Data Exchange (ETDEWEB)

    Earle, T.C.; Lindell, M.K.; Rankin, W.L.

    1981-07-01

    Public acceptance of radioactive waste management alternatives depends in part on public perception of the associated risks. Three aspects of those perceived risks were explored in this study: (1) synthetic measures of risk perception based on judgments of probability and consequences; (2) acceptability of hypothetical radioactive waste policies, and (3) effects of human values on risk perception. Both the work on synthetic measures of risk perception and on the acceptability of hypothetical policies included investigations of three categories of risk: (1) Short-term public risk (affecting persons living when the wastes are created), (2) Long-term public risk (affecting persons living after the time the wastes were created), and (3) Occupational risk (affecting persons working with the radioactive wastes). The human values work related to public risk perception in general, across categories of persons affected. Respondents were selected according to a purposive sampling strategy.

  20. Humans vs Hardware: The Unique World of NASA Human System Risk Assessment

    Science.gov (United States)

    Anton, W.; Havenhill, M.; Overton, Eric

    2016-01-01

    Understanding spaceflight risks to crew health and performance is a crucial aspect of preparing for exploration missions in the future. The research activities of the Human Research Program (HRP) provide substantial evidence to support most risk reduction work. The Human System Risk Board (HSRB), acting on behalf of the Office of Chief Health and Medical Officer (OCHMO), assesses these risks and assigns likelihood and consequence ratings to track progress. Unfortunately, many traditional approaches in risk assessment such as those used in the engineering aspects of spaceflight are difficult to apply to human system risks. This presentation discusses the unique aspects of risk assessment from the human system risk perspective and how these limitations are accommodated and addressed in order to ensure that reasonable inputs are provided to support the OCHMO's overall risk posture for manned exploration missions.

  1. Heavy Metal Contamination in Soil and Brown Rice and Human Health Risk Assessment near Three Mining Areas in Central China

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2017-01-01

    Full Text Available Background. Metal mining and waste discharge lead to regional heavy metal contamination and attract major concern because of the potential risk to local residents. Methods. This research was conducted to determine lead (Pb, cadmium (Cd, arsenic (As, manganese (Mn, and antimony (Sb concentrations in soil and brown rice samples from three heavy metal mining areas in Hunan Province, central China, and to assess the potential health risks to local inhabitants. Results. Local soil contamination was observed, with mean concentrations of Cd, Pb, Sb, and As of 0.472, 193.133, 36.793, and 89.029 mg/kg, respectively. Mean concentrations of Cd, Pb, Sb, Mn, and As in brown rice were 0.103, 0.131, 5.175, 6.007, and 0.524 mg/kg, respectively. Daily intakes of Cd, As, Sb, Pb, and Mn through brown rice consumption were estimated to be 0.011, 0.0002, 0.004, 0.0001, and 0.0003 mg/(kg/day, respectively. The combined hazard index for the five heavy metals was 22.5917, and the total cancer risk was 0.1773. Cd contributed most significantly to cancer risk, accounting for approximately 99.77% of this risk. Conclusions. The results show that potential noncarcinogenic and carcinogenic health risks exist for local inhabitants and that regular monitoring of pollution to protect human health is urgently required.

  2. Polycyclic aromatic hydrocarbons (PAHs) in urban soils of the megacity Shanghai: occurrence, source apportionment and potential human health risk.

    Science.gov (United States)

    Wang, Xue-Tong; Miao, Yi; Zhang, Yuan; Li, Yuan-Cheng; Wu, Ming-Hong; Yu, Gang

    2013-03-01

    A comprehensive investigation was conducted to the urban soil in the megacity Shanghai in order to assess the levels of PAHs and potential risks to human health, to identify and quantitatively assess source contributions to the soil PAHs. A total of 57 soil samples collected in main urban areas of Shanghai, China were analyzed for 26 PAHs including highly carcinogenic dibenzopyrene isomers. The total concentrations ranged from 133 to 8,650 ng g for ΣPAHs and 83.3 to 7,220 ng g for ΣPAHs, with mean values of 2420 and 1,970 ng g, respectively. DBalP and DBaeP may serve as markers for diesel vehicle emission, while DBahP is a probable marker of coke tar as distinct from diesel emissions. Six sources in Shanghai urban area were identified by PMF model; their relative contributions to the total soil PAH burden were 6% for petrogenic sources, 21% for coal combustion, 13% for biomass burning, 16% for creosote, 23% for coke tar related sources and 21% for vehicular emissions, respectively. The benzo[a]pyrene equivalent (BaP) concentrations ranged from 48.9-2,580 ng g for ΣPAHs, 7.02-869 ng g for ΣPAHs and 35.7-1,990 ng g for ΣDBPs. The BaP concentrations of ΣDBPs made up 72% of ΣPAHs. Nearly half of the soil samples showed concentrations above the safe BaP value of 600 ng g. Exposure to these soils through direct contact probably poses a significant risk to human health from carcinogenic effects of soil PAHs. The index of additive cancer risk (IACR) values in almost one third of urban soil samples were more than the safe value of 1.0, indicating these urban soil PAHs in the study area may pose a potential threat to potable groundwater water quality from leaching of carcinogenic PAH mixtures from soil.

  3. Excretory/secretory products of the carcinogenic liver fluke are endocytosed by human cholangiocytes and drive cell proliferation and IL6 production.

    Science.gov (United States)

    Chaiyadet, Sujittra; Smout, Michael; Johnson, Michael; Whitchurch, Cynthia; Turnbull, Lynne; Kaewkes, Sasithorn; Sotillo, Javier; Loukas, Alex; Sripa, Banchob

    2015-10-01

    Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south

  4. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Beyersmann, Detmar [University of Bremen (Germany). Biochemistry, Department of Biology and Chemistry; Hartwig, Andrea [Technical University of Berlin (Germany). Institute of Food Technology and Food Chemistry

    2008-08-15

    Mechanisms of carcinogenicity are discussed for metals and their compounds, classified as carcinogenic to humans or considered to be carcinogenic to humans: arsenic, antimony, beryllium, cadmium, chromium, cobalt, lead, nickel and vanadium. Physicochemical properties govern uptake, intracellular distribution and binding of metal compounds. Interactions with proteins (e.g., with zinc finger structures) appear to be more relevant for metal carcinogenicity than binding to DNA. In general, metal genotoxicity is caused by indirect mechanisms. In spite of diverse physicochemical properties of metal compounds, three predominant mechanisms emerge: (1) interference with cellular redox regulation and induction of oxidative stress, which may cause oxidative DNA damage or trigger signaling cascades leading to stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic instability and accumulation of critical mutations; (3) deregulation of cell proliferation by induction of signaling pathways or inactivation of growth controls such as tumor suppressor genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction of vanadate with phosphate binding sites of protein phosphatases. (orig.)

  5. Non—Genotoxic Carcinogens.Approaches to Their Rish Assessment

    Institute of Scientific and Technical Information of China (English)

    J.A.CASTRO; M.I.DiazGomez; 等

    1993-01-01

    Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment.In turn,chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms.There were described in literature several simple rapid and inexpensive short term ests to reasonably predict the genotoxic nature of chemicals but in contrast,there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their rish assessment.In addition,there are conflictive opinions about rish assessment needs for both classes of carcinogens.Some workers elieve that for non-genotoxic carcinogens,thresholds for exposure can be drawn while others do not.In this review,the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.

  6. Metabolism of benzo(a)pyrene, N-nitrosomethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus

    DEFF Research Database (Denmark)

    1979-01-01

    The wide variation in the world-wide incidence of esophageal carcinoma suggests that environmental agents including chemicals cause this cancer. Since the interaction between chemical procarcinogens and human esophagus has not been studied previously, we examined the metabolic fate of benzo......(a)pyrene (BP), N-nitrosodimethylamine (DMN), and A/-nitrosopyrrolidine in cultured nontumorous esophagus from two patients with and six patients without esophageal carcinoma. Esophageal explants were cultured in a chemically defined medium for 7 days prior to adding [3H]BP (1.5 JUM),[14C]DMN (100 /IM), or [14C...

  7. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets.

    Science.gov (United States)

    Rider, Cynthia V; Nyska, Abraham; Cora, Michelle C; Kissling, Grace E; Smith, Cynthia; Travlos, Gregory S; Hejtmancik, Milton R; Fomby, Laurene M; Colleton, Curtis A; Ryan, Michael J; Kooistra, Linda; Morrison, James P; Chan, Po C

    2014-07-01

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use.

  8. Meeting the coming organizational risk challenges in human resources

    Directory of Open Access Journals (Sweden)

    Zakić Nebojša

    2016-01-01

    Full Text Available The research presented in this paper concerns challenges of organizational risk in the field of human resources. Research goals are to determine the degree of importance and influence of human risks in order to achieve a more favorable environment for successful business. The empirical research has been conducted in Serbia during 2015, with a sample of 43 companies from the Processing industry. There were mathematical and statistical methods, multiple regression analysis and logistic regression used. Group's core results showed that over 80% of production companies are aware of the human resources risks and their importance for the business. The contribution of this paper is to prove the scientific significance of the upcoming risks of human resources establishing theoretical and empirical knowledge about the need to improve organization approach to managing these risks.

  9. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats.

    Science.gov (United States)

    Patlolla, Jagan M R; Zhang, Yuting; Li, Qian; Steele, Vernon E; Rao, Chinthalapally V

    2012-01-01

    Omeprazole is a proton pump inhibitor, a widely used drug to treat ulcers and gastroesophageal refluxdisease. We have evaluated colon cancer chemopreventive properties of omeprazole using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in male F344 rats and analyzed cell growth inhibition and apoptosis induction in human colon cancer cells. Five-week-old male F344 rats were fed a control or experimental diet containing two doses of omeprazole (200 and 400 ppm). After one week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for two weeks). Rats continued on experimental diets for seven more weeks before being sacrificed. Colons were histopathologically evaluated for ACF. Human colon cancer HCT-116 and HCA-7 cells treated with omeprazole were evaluated for different markers associated with proliferation and apoptotic markers using Western blot technique. Rats fed with 200 and 400 ppm of omeprazole significantly suppressed total colonic ACF formation (~30%, Pcancer cell lines HCT-116 and HCA-7 cells resulted in induction of p21waf1/cip1 and decreased the expression of anti-apoptotic proteins Bcl-2, Bcl-XL and survivin in a dose-dependent manner. Anticancer properties observed in colon cancer cell lines suggest that omeprazole may induce key signaling molecules of antiproliferation and inhibition of anti-apoptotic proteins.

  10. Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines.

    Science.gov (United States)

    Hecht, Stephen S; Stepanov, Irina; Carmella, Steven G

    2016-01-19

    Lung cancer is the leading cause of cancer death in the world, and cigarette smoking is its main cause. Oral cavity cancer is another debilitating and often fatal cancer closely linked to tobacco product use. While great strides have been made in decreasing tobacco use in the United States and some other countries, there are still an estimated 1 billion men and 250 million women in the world who are cigarette smokers and there are hundreds of millions of smokeless tobacco users, all at risk for cancer. Worldwide, lung cancer kills about three people per minute. This Account focuses on metabolites and biomarkers of two powerful tobacco-specific nitrosamine carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN), considered to be among the main causes of lung cancer and oral cavity cancer in people who use tobacco products. Three properties of NNK and NNN are critical for successful biomarker studies: they are present in all tobacco products, they are tobacco-specific and are not found in any other product, and they are strong carcinogens. NNK and NNN are converted in humans to urinary metabolites that can be quantified by mass spectrometry as biomarkers of exposure to these carcinogens. They are also metabolized to diazonium ions and related electrophiles that react with DNA to form addition products that can be detected and quantified by mass spectrometry. These urinary metabolites and DNA addition products can serve as biomarkers of exposure and metabolic activation, respectively. The biomarkers of exposure, in particular the urinary NNK metabolites 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, have been extensively applied to document tobacco-specific lung carcinogen uptake in smokers and nonsmokers exposed to secondhand tobacco smoke. Highly sensitive mass spectrometric methods have been developed for quantitative analysis of these NNK metabolites as well as metabolites of NNN in human urine

  11. Human activities change marine ecosystems by altering predation risk.

    Science.gov (United States)

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. © 2015 John Wiley & Sons Ltd.

  12. Human health risk assessment of heavy metals in urban stormwater.

    Science.gov (United States)

    Ma, Yukun; Egodawatta, Prasanna; McGree, James; Liu, An; Goonetilleke, Ashantha

    2016-07-01

    Toxic chemical pollutants such as heavy metals (HMs) are commonly present in urban stormwater. These pollutants can pose a significant risk to human health and hence a significant barrier for urban stormwater reuse. The primary aim of this study was to develop an approach for quantitatively assessing the risk to human health due to the presence of HMs in stormwater. This approach will lead to informed decision making in relation to risk management of urban stormwater reuse, enabling efficient implementation of appropriate treatment strategies. In this study, risks to human health from heavy metals were assessed as hazard index (HI) and quantified as a function of traffic and land use related parameters. Traffic and land use are the primary factors influencing heavy metal loads in the urban environment. The risks posed by heavy metals associated with total solids and fine solids (heavy metal does not pose a significant risk, the presence of multiple heavy metals could be detrimental to human health. These findings suggest that stormwater guidelines should consider the combined risk from multiple heavy metals rather than the threshold concentration of an individual species. Furthermore, it was found that risk to human health from heavy metals in stormwater is significantly influenced by traffic volume and the risk associated with stormwater from industrial areas is generally higher than that from commercial and residential areas.

  13. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    Science.gov (United States)

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  14. Human Health Risks Assessment Associated with Polychlorinated Biphenyls (PCBs) in Soil from Different Contaminated Areas of Mexico.

    Science.gov (United States)

    Pérez-Maldonado, Iván N; Ochoa Martínez, Ángeles C; Ruíz-Vera, Tania; Orta-García, Sandra T; Varela-Silva, José A

    2017-08-03

    Recent studies have documented environmental contamination by PCBs in soil from different areas in Mexico (industrial, mining, and urban sites). However, the real significance of that soil contamination has not been established. Therefore, the aim of this study was to perform a human health risk assessment (Monte Carlos simulation) to evaluate the probable toxic effects of soils contaminated with PCBs on children in four sites in Mexico. A high non-carcinogenic risk (total nHQ = 1.1E+01; if nHQ ≥1, hazardous health effects cannot be ruled out) was found in Alpuyeca, Morelos, Mexico. Moreover, the total CR (cancer risk) found in Alpuyeca, Morelos is of concern (total CR = 5.1E-03), being that a cut-point of 1.0E-06 has been suggested as a safe level for cancer risk. Taking into consideration the data shown in this research, we conclude that a strategy to protect human health is necessary for the assessed sites.

  15. Spatial gradient of human health risk from exposure to trace elements and radioactive pollutants in soils at the Puchuncaví-Ventanas industrial complex, Chile.

    Science.gov (United States)

    Salmani-Ghabeshi, S; Palomo-Marín, M R; Bernalte, E; Rueda-Holgado, F; Miró-Rodríguez, C; Cereceda-Balic, F; Fadic, X; Vidal, V; Funes, M; Pinilla-Gil, E

    2016-11-01

    The Punchuncaví Valley in central Chile, heavily affected by a range of anthropogenic emissions from a localized industrial complex, has been studied as a model environment for evaluating the spatial gradient of human health risk, which are mainly caused by trace elemental pollutants in soil. Soil elemental profiles in 121 samples from five selected locations representing different degrees of impact from the industrial source were used for human risk estimation. Distance to source dependent cumulative non-carcinogenic hazard indexes above 1 for children (max 4.4 - min 1.5) were found in the study area, ingestion being the most relevant risk pathway. The significance of health risk differences within the study area was confirmed by statistical analysis (ANOVA and HCA) of individual hazard index values at the five sampling locations. As was the dominant factor causing unacceptable carcinogenic risk levels for children (industrial complex, whereas the risk was just in the tolerable range (10(-6) - 10(-4)) for children and adults in the rest of the sampling locations at the study area. Furthermore, we assessed gamma ray radiation external hazard indexes and annual effective dose rate from the natural radioactivity elements ((226)Ra, (232)Th and (40)K) levels in the surface soils of the study area. The highest average values for the specific activity of (232)Th (31 Bq kg(-1)), (40)K (615 Bq kg(- 1)), and (226)Ra (25 Bq kg(-1)) are lower than limit recommended by OECD, so no significant radioactive risk was detected within the study area. In addition, no significant variability of radioactive risk was observed among sampling locations.

  16. 76 FR 71037 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Science.gov (United States)

    2011-11-16

    ... HUMAN SERVICES Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens... Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS); National Institutes... (see ADDRESSES). Dated: November 8, 2011. John R. Bucher, Associate Director, National...

  17. Towards health impact assessment of drinking-water privatization--the example of waterborne carcinogens in North Rhine-Westphalia (Germany).

    Science.gov (United States)

    Fehr, Rainer; Mekel, Odile; Lacombe, Martin; Wolf, Ulrike

    2003-01-01

    Worldwide there is a tendency towards deregulation in many policy sectors - this, for example, includes liberalization and privatization of drinking-water management. However, concerns about the negative impacts this might have on human health call for prospective health impact assessment (HIA) on the management of drinking-water. On the basis of an established generic 10-step HIA procedure and on risk assessment methodology, this paper aims to produce quantitative estimates concerning health effects from increased exposure to carcinogens in drinking-water. Using data from North Rhine-Westphalia in Germany, probabilistic estimates of excess lifetime cancer risk, as well as estimates of additional cases of cancer from increased carcinogen exposure levels are presented. The results show how exposure to contaminants that are strictly within current limits could increase cancer risks and case-loads substantially. On the basis of the current analysis, we suggest that with uniform increases in pollutant levels, a single chemical (arsenic) is responsible for a large fraction of expected additional risk. The study also illustrates the uncertainty involved in predicting the health impacts of changes in water quality. Future analysis should include additional carcinogens, non-cancer risks including those due to microbial contamination, and the impacts of system failures and of illegal action, which may be increasingly likely to occur under changed management arrangements. If, in spite of concerns, water is privatized, it is particularly important to provide adequate surveillance of water quality.

  18. Environmental levels of PCDD/Fs and metals around a cement plant in Catalonia, Spain, before and after alternative fuel implementation. Assessment of human health risks

    Energy Technology Data Exchange (ETDEWEB)

    Rovira, Joaquim [Laboratory of Toxicology and Environmental Health, School of Medicine, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Catalonia (Spain); Nadal, Martí, E-mail: marti.nadal@urv.cat [Laboratory of Toxicology and Environmental Health, School of Medicine, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Schuhmacher, Marta [Laboratory of Toxicology and Environmental Health, School of Medicine, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Països Catalans 26, 43007 Tarragona, Catalonia (Spain); Domingo, José L. [Laboratory of Toxicology and Environmental Health, School of Medicine, Universitat Rovira i Virgili, Sant Llorenç 21, 43201 Reus, Catalonia (Spain)

    2014-07-01

    The concentrations of As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, Tl, V, and Zn, and the levels of polychlorinated dibenzo-p-dioxins and dibenzofurans were determined in samples of soil, vegetation, and air, collected in the vicinity of a cement plant (Catalonia, Spain), before (January 2011 and July 2011) and after (January 2012 and June 2013) alternative fuel partial substitution (fossil fuels by sewage sludge). Seven sampling points were selected at different directions and distances to the facility including two background sampling points. The results were used to assess the health risk assessment for the population living near the facility. Only few significant differences were found before and after alternative fuel partial substitution (Mn in soils and Cd in vegetation). Non-carcinogenic risks were below the safety threshold (HQ < 1), while carcinogenic risks were below 10{sup −5}, or exceeding slightly that value, always in the range considered as assumable (10{sup −6}–10{sup −4}). - Highlights: • The environmental impact of a cement plant using alternative fuel was monitored. • No significant differences in most pollutants were noted after the fuel change. • Traffic has a notable influence on the environmental levels of PCDD/Fs and metals. • Human health risks were below safety thresholds regardless of the used fuel.

  19. A review of mammalian carcinogenicity study design and potential effects of alternate test procedures on the safety evaluation of food ingredients.

    Science.gov (United States)

    Hayes, A W; Dayan, A D; Hall, W C; Kodell, R L; Williams, G M; Waddell, W D; Slesinski, R S; Kruger, C L

    2011-06-01

    of test procedures, dose selection, histopathology procedures, application of historical control data, statistical evaluations and whether statistical extrapolations are supported by, or are beyond the limits of, the data generated. Without due consideration, there can be result conflicting data interpretations and uncertainty about the relevance of a study's results to human risk. This paper discusses the critical elements of rodent (rat) carcinogenicity studies, particularly with respect to the study of food ingredients. It also highlights study practices and procedures that can detract from the appropriate evaluation of human relevance of results, indicating the importance of adherence to international consensus protocols, such as those detailed by OECD.

  20. Risk managment of complex aquifers contaminated by chemical mixtures : numerical tools and human health risk assessment

    OpenAIRE

    Henri, Christopher

    2015-01-01

    Human impact on groundwater resources has led to a rapid growth of social concerns worldwide owing to an increasing presence of toxic chemicals released in the subsurface. Risk assessment provides the scientific tool needed to quantify the actual thread that these potential hazards pose to human health. Specifically, risk analysis enables decision makers to answer: What can happen? How likely is it to happen? What can be the consequences? Risk assessment is in this context essential. However,...

  1. Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: a risk to human health?

    Science.gov (United States)

    Nohynek, Gerhard J; Dufour, Eric K

    2012-07-01

    Personal care products (PCP) often contain micron- or nano-sized formulation components, such as nanoemulsions or microscopic vesicles. A large number of studies suggest that such vesicles do not penetrate human skin beyond the superficial layers of the stratum corneum. Nano-sized PCP formulations may enhance or reduce skin absorption of ingredients, albeit at a limited scale. Modern sunscreens contain insoluble titanium dioxide (TiO₂) or zinc oxide (ZnO) nanoparticles (NP), which are efficient filters of UV light. A large number of studies suggest that insoluble NP do not penetrate into or through human skin. A number of in vivo toxicity tests, including in vivo intravenous studies, showed that TiO₂ and ZnO NP are non-toxic and have an excellent skin tolerance. Cytotoxicity, genotoxicity, photo-genotoxicity, general toxicity and carcinogenicity studies on TiO₂ and ZnO NP found no difference in the safety profile of micro- or nano-sized materials, all of which were found to be non-toxic. Although some published in vitro studies on insoluble nano- or micron-sized particles suggested cell uptake, oxidative cell damage or genotoxicity, these data are consistent with those from micron-sized particles and should be interpreted with caution. Data on insoluble NP, such as surgical implant-derived wear debris particles or intravenously administered magnetic resonance contrast agents suggest that toxicity of small particles is generally related to their chemistry rather than their particle size. Overall, the weight of scientific evidence suggests that insoluble NP used in sunscreens pose no or negligible risk to human health, but offer large health benefits, such as the protection of human skin against UV-induced skin ageing and cancer.

  2. Longitudinal Analysis of Carcinogenic Human Papillomavirus Infection and Associated Cytologic Abnormalities in the Guanacaste Natural History Study: Looking Ahead to Cotesting

    Science.gov (United States)

    Rodriguez, Ana C.; Burk, Robert D.; Hildesheim, Allan; Herrero, Rolando; Wacholder, Sholom; Hutchinson, Martha; Schiffman, Mark

    2012-01-01

    Background. Few studies have addressed the timing of cervical cytologic abnormalities and human papillomavirus (HPV) positivity during the course of an infection. It remains largely unknown how infections detected by HPV and cytology wax and wane relative to each other. The aim of this analysis was to assess the longitudinal relationship of abnormal cytology and HPV positivity in a 7-year prospective study of 2500 women in Guanacaste, Costa Rica. Methods. At each semiannual or annual visit, cervical specimens were screened using liquid-based cytology and tested for >40 HPV types with use of MY09/MY11 L1 degenerate primer polymerase chain reaction–based methods. On the basis of previous work, we separated prevalent and newly detected infections in younger and older women. Results. Among newly detected HPV- and/or cytology-positive events, HPV and cytology appeared together ∼60% of the time; when discordant, HPV tended to appear before cytology in younger and older women. Combining newly and prevalently detected events, HPV and cytology disappeared at the same time >70% of the time. When discordant, HPV tended to disappear after cytology in younger and older women. Conclusions. Detection of HPV DNA and associated cytological abnormalities tend to come and leave together; however, when discordant, detection of HPV DNA tends to precede and/or last longer than associated cytologic abnormalities. PMID:22147792

  3. Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase η.

    Science.gov (United States)

    Patra, Amritraj; Politica, Dustin A; Chatterjee, Arindom; Tokarsky, E John; Suo, Zucai; Basu, Ashis K; Stone, Michael P; Egli, Martin

    2016-11-03

    The environmental pollutant 3-nitrobenzanthrone produces bulky aminobenzanthrone (ABA) DNA adducts with both guanine and adenine nucleobases. A major product occurs at the C8 position of guanine (C8-dG-ABA). These adducts present a strong block to replicative polymerases but, remarkably, can be bypassed in a largely error-free manner by the human Y-family polymerase η (hPol η). Here, we report the crystal structure of a ternary Pol⋅DNA⋅dCTP complex between a C8-dG-ABA-containing template:primer duplex and hPol η. The complex was captured at the insertion stage and provides crucial insight into the mechanism of error-free bypass of this bulky lesion. Specifically, bypass involves accommodation of the ABA moiety inside a hydrophobic cleft to the side of the enzyme active site and formation of an intra-nucleotide hydrogen bond between the phosphate and ABA amino moiety, allowing the adducted guanine to form a standard Watson-Crick pair with the incoming dCTP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Human population density and extinction risk in the world's carnivores.

    Directory of Open Access Journals (Sweden)

    Marcel Cardillo

    2004-07-01

    Full Text Available Understanding why some species are at high risk of extinction, while others remain relatively safe, is central to the development of a predictive conservation science. Recent studies have shown that a species' extinction risk may be determined by two types of factors: intrinsic biological traits and exposure to external anthropogenic threats. However, little is known about the relative and interacting effects of intrinsic and external variables on extinction risk. Using phylogenetic comparative methods, we show that extinction risk in the mammal order Carnivora is predicted more strongly by biology than exposure to high-density human populations. However, biology interacts with human population density to determine extinction risk: biological traits explain 80% of variation in risk for carnivore species with high levels of exposure to human populations, compared to 45% for carnivores generally. The results suggest that biology will become a more critical determinant of risk as human populations expand. We demonstrate how a model predicting extinction risk from biology can be combined with projected human population density to identify species likely to move most rapidly towards extinction by the year 2030. African viverrid species are particularly likely to become threatened, even though most are currently considered relatively safe. We suggest that a preemptive approach to species conservation is needed to identify and protect species that may not be threatened at present but may become so in the near future.

  5. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Bryan L. Stegelmeier

    2016-11-01

    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  6. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Science.gov (United States)

    Stegelmeier, Bryan L.; Colegate, Steven M.; Brown, Ammon W.

    2016-01-01

    Dehydropyrrolizidine alkaloid (DHPA)-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health. PMID:27916846

  7. Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Elizabeth Tahanian

    2011-01-01

    Full Text Available Elizabeth Tahanian, Sabrina Peiro, Borhane AnnabiLaboratoire d'Oncologie Moléculaire, Centre de Recherche BioMED, Département de Chimie, Université du Québec à Montréal, Montréal, Québec, CanadaAbstract: Solid tumor development requires angiogenesis and is correlated to the expression of inflammatory markers through cellular metabolic and energetic adaptation. While high glycolysis rates enable the cancer cell compartment to generate adenosine triphosphate (ATP, very little is known about the impact of low intracellular ATP concentrations within the vascular endothelial cell compartment, which is responsible for tumor angiogenesis. Here, we investigated the effect of 2-deoxy-D-glucose (2-DG, a glucose analog that inhibits glycolysis through intracellular ATP depletion, on human brain microvascular endothelial cell (HBMEC angiogenic properties. While preformed capillaries remained unaffected, we found that in vitro tubulogenesis was dose-dependently decreased by 2-DG and that this correlated with reduced intracellular ATP levels. Procarcinogenic signaling was induced with phorbol 12-myristate 13-acetate (PMA and found to trigger the proinflammatory marker cyclooxygenase-2 (COX-2 and endoplasmic reticulum (ER stress marker GRP78 expression, whose inductions were potentiated when PMA was combined with 2-DG treatment. Inversely, PMA-induced matrix-metalloproteinase-9 (MMP-9 gene expression and protein secretion were abrogated in the presence of 2-DG, and this can be partially explained by reduced nuclear factor-κB signaling. Collectively, we provide evidence for an intracellular ATP requirement in order for tubulogenesis to occur, and we link increases in ER stress to inflammation. A better understanding of the metabolic adaptations of the vascular endothelial cells that mediate tumor vascularization will help the development of new drugs and therapies.Keywords: endoplasmic reticulum stress, MMP-9, COX-2, 2-deoxy-D-glucose, endothelial

  8. Carcinogenicity and mechanistic insights on the behavior of epoxides and epoxide-forming chemicals.

    Science.gov (United States)

    Melnick, Ronald L

    2002-12-01

    Many epoxides and their precursors are high production volume chemicals that have major uses in the polymer industry and as intermediates in the manufacture of other chemicals. Several of these chemicals were demonstrated to be carcinogenic in laboratory animal studies conducted by the Ramazzini Foundation (e.g., vinyl chloride, acrylonitrile, styrene, styrene oxide, and benzene) and by the National Toxicology Program (e.g., ethylene oxide, 1,3-butadiene, isoprene, chloroprene, acrylonitrile, glycidol, and benzene). The most common sites of tumor induction were lung, liver, harderian gland, and circulatory system in mice; Zymbal's gland and brain in rats; and mammary gland and forestomach in both species. Differences in cancer outcome among studies of epoxide chemicals may be related to differences in study design (e.g., dose, duration, and route of exposure; observation period; animal strains), as well as biological factors affecting target organ dosimetry of the DNA-reactive epoxide (toxicokinetics) and tissue response (toxicodynamics). N7-Alkylguanine, N1-alkyladenine, and cyclic etheno adducts, as well as K-ras and p53 mutations, have been detected in animals and/or workers exposed to several of these chemicals. The classifications of these chemical carcinogens by IARC and NTP are based on animal and human data and results of mechanistic studies. Reducing occupational and environmental exposures to these chemicals will certainly reduce human cancer risks.

  9. Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation.

    Science.gov (United States)

    Afshari, C A; Nuwaysir, E F; Barrett, J C

    1999-10-01

    One major challenge facing today's cancer researchers and toxicologists is the development of new approaches for the identification of carcinogens and other environmental hazards. Here, we describe the potential impact of emerging technologies for measuring gene expression profiles on carcinogen identification and on the general field of toxicology. An example of one of these technologies is the use of cDNA microarray chips. We provide an overview to the key questions that are confronting investigators charged with determining the relative safety of natural or synthetic chemicals to which humans are exposed, followed by a discussion of how cDNA microarray technology may be applied to these questions. Gene chip technology is still a relatively new technology, and only a handful of studies have demonstrated its utility. However, as the technical hurdles to development are passed, the use of this methodology in addressing the questions raised here will be critical to increase the sensitivity of detection of the potential toxic effects of environmental chemicals and to understand their risks to humans.

  10. MINI REVIEW - EPIGENETIC PROCESSES AND CANCER RISK ASSESSMENT

    Science.gov (United States)

    Abstract: The U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment encourages the use of mechanistic data in the assessment of human cancer risk at low (environmental) exposure levels. The key events that define a particular mode of action for tumor fo...

  11. Disaster risk mitigation – why human rights matter

    Directory of Open Access Journals (Sweden)

    Walter Kälin

    2008-10-01

    Full Text Available Existing human rights obligations already require states totake measures to mitigate the risks of natural or man-madedisasters – including those due to climate change – and thusto prevent displacement.

  12. Framework for Human Health Risk Assessment to Inform Decision Making

    Science.gov (United States)

    The purpose of this document is to describe a Framework for conducting human health risk assessments that are responsive to the needs of decision‐making processes in the U.S. Environmental Protection Agency (EPA).

  13. On the issue of higher human sensitivity to carcinogenic substances in early childhood; Zur Frage einer hoeheren Empfindlichkeit von Kindern gegenueber krebserzeugenden Stoffen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, K. [comp.

    1998-09-01

    Age-dependent carcinogenesis in humans has been proven with high probability for a number of substances investigated within one or several model systems. Sometimes, very high tumor incidence after short exposure time was observed. Extreme differences were found in some models. (A) Vinyl chloride, Maltoni et al.,1981: 6000 ppm, hepatic angiosarcoma incidence: - Exposure for 4 weeks, from day 1: 40.5 %, - exposure for 4 weeks, from week 13: 0%, - exposure for 52 weeks, from week 13: 22%. Hepatoma incidence: - Exposure for 4 weeks, from day 1: 47.6%, exposure for 4 weeks, from week 13: 0%, exposure for 52 weeks, from week 13: 1.7%. (B) Diethyl nitrosamine, Dyroff et al., 1986: (DEN + phenobarbital), hepatic carcinoma after exposure of rats for 6 weeks: - as from 4 weeks of age: 100% incidence, - as from 8 weeks of age: 0% incidence. (C) Benzopyrene, Vesselinovitch et al., 1975: Hepatic tumor incidence after single, parenteral administration to rats: - at day 1: males: 81%, females: 18%, - at day 42: males: 9%, females: 0%. As is shown by the study on vinyl chloride by Maltoni et al., the same exposure concentration may lead to higher tumor incidence in young animals after short exposure times than it does in long-term experiments with adult animals. Genetic toxicity was detected for all substances, except for saccharin. So it can be assumed that the mechanism of carcinogenesis has an essential influence on the age-dependence. This conclusion agrees well with mechanistic approaches. (orig./CB) [German] Fuer eine Reihe von Schadstoffen ist eine Altersabhaengigkeit der Kanzerogenese mit hoher Wahrscheinlichkeit in einem oder mehreren Modellsystemen gezeigt worden. Dabei wurden zum Teil bereits nach kurzer Expositionszeit sehr hohe Tumorausbeuten erzielt. Extreme Unterschiede wurden in folgenden Modellen beobachtet. (A) Vinylchlorid, Maltoni et al., 1981: 6000 ppm, Inzidenz Leberangiosarkome: - Exposition ueber 4 Wochen ab Tag 1: 40,5%, - Exposition ueber 4 Wochen ab 13

  14. The Role of Tobacco-Derived Carcinogens in Pancreas Cancer

    OpenAIRE

    Lochan, Rajiv; Reeves, Helen L.; Daly, Anne K.; Charnley, Richard M

    2011-01-01

    The extremely poor outcome from pancreas cancer is well known. However, its aetiology less well appreciated, and the molecular mechanisms underlying this are poorly understood. Tobacco usage is one of the strongest risk factors for this disease, and this is a completely avoidable hazard. In addition, there are well described hereditary diseases which predispose, and familial pancreas cancer. We have sought here to summarise the role of tobacco-derived carcinogens and the mode of their tumorig...

  15. 76 FR 39399 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability

    Science.gov (United States)

    2011-07-06

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability... availability of EPA's preliminary human health risk assessment for the registration review of chlorpyrifos and... comprehensive preliminary human health risk assessment for all chlorpyrifos uses. After reviewing comments...

  16. 76 FR 52945 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment...

    Science.gov (United States)

    2011-08-24

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment... availability of the chlorpyrifos registration review; preliminary human health risk assessment. This document... for the chlorpyrifos reregistration review, preliminary human health risk assessment, established in...

  17. Assessing human health risk in the USDA forest service

    Energy Technology Data Exchange (ETDEWEB)

    Hamel, D.R. [Department of Agriculture-Forest Service, Washington, DC (United States)

    1990-12-31

    This paper identifies the kinds of risk assessments being done by or for the US Department of Agriculture (USDA) Forest Service. Summaries of data sources currently in use and the pesticide risk assessments completed by the agency or its contractors are discussed. An overview is provided of the agency`s standard operating procedures for the conduct of toxicological, ecological, environmental fate, and human health risk assessments.

  18. Trichloroethylene risk assessment: Relevance of inter-individual differences

    NARCIS (Netherlands)

    Vermeulen, N.P.E.; Bladeren, van P.J.

    2001-01-01

    Interindividual variability in the disposition and effects of xenobiotics in humans and related inter-species differences should play a major role in human risk assessment. In particular for low-dose exposures to potentially carcinogenic compounds, novel tools and concepts are necessary to assess

  19. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.

    Science.gov (United States)

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W

    2011-10-01

    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.

  20. Possibilities and limitations of sup 1 H and sup 13 C nuclear magnetic resonance spectroscopy for the identification and the quantitative determination of some naturally occurring carcinogenic risk factors. [Senecio vulgaris; Senecio vernalis; Senecio jacobaea; Euphorbia ingens

    Energy Technology Data Exchange (ETDEWEB)

    Pieters, L.

    1988-01-01

    The aim of this work was to develop a phytochemical screening method for some selected carcinogenic or tumor-promoting principles in higher plants. The pyrrolizidine alkaloids from some Senecio species (Compositae or Asteraceae), and the diterpene ester from Croton tiglium L. and Euphorbia ingens E. Mey (Euphorbiaceae) were chosen as representatives of both groups. The possibilities and limitations of {sup 1}H and {sup 13}C nuclear magnetic resonance spectroscopy ({sup 1}H and {sup 13}C NMR) for the analysis of mixtures of carcinogenic pyrrolizidine alkaloids were compared with high performance liquid chromatography, and gas chromatography with high performance liquid chromatography, and gas chromatography was well as gas chromatography - mass spectrometry. Senecio vulgaris L., Senecio vernalis Waldst. and Kit. and Senecio jacobaea L. were investigated.

  1. A population-based cross-sectional study of age-specific risk factors for high risk human papillomavirus prevalence in rural Nigeria

    Directory of Open Access Journals (Sweden)

    Clarke Megan A

    2011-07-01

    Full Text Available Abstract Background Cervical cancer, caused by persistent infection with carcinogenic human papillomavirus (HR-HPV, is particularly prevalent in Sub-Saharan Africa and is associated with a high mortality rate. Some studies in West Africa, including our own, have found unusually high HR-HPV across all ages with a slight peak in older women. This increased prevalence at older ages may complicate screen-and-treat programs, which are implemented in regions where HPV prevalence declines with age and typically target women between 30-49 years. A better understanding of the determinants of high HR-HPV prevalence at older ages is needed. The goal of this study is to explore risk factors for HR-HPV prevalence by age among women in our population-based study in Irun, a rural town in southwestern Nigeria. Methods 1,420 women were administered a clinic-based questionnaire regarding sexual and reproductive behavior, marital status (including co-wives, and malaria exposure. Logistic regression compared questionnaire responses and PCR positivity for a set of 13 carcinogenic HR-HPV types. Results were stratified by age (15-29, 30-45, 46-55, and 56+ years. Results Birth control use and age at first pregnancy were associated with HR-HPV (p-value = 0.03 and 0.05, respectively. Early age at sexual debut and multiple sex partners were risks for HR-HPV, but did not reach significance (p-value = 0.1 and 0.07, respectively. Neither self-reported malaria nor presence of co-wives in the household was associated with HR-HPV (p-value = 0.85 and 0.24, respectively. In age sub-categories, early age at sexual debut was a significant risk factor for HR-HPV among women 35-45 years (p-value = 0.02. Early age at first pregnancy remained a significant risk factor for women aged 56+ years (p-value = 0.04. Greater than 2 sex partners and use of birth control were associated (though not significantly with HR-HPV in women aged 30-45 (p-value = 0.08, respectively. Conclusions In this

  2. Hydrocarbon insecticides: their risks for environment and human health.

    Science.gov (United States)

    El-Bahnasawy, Mamdouh M; Mohammad, Amina El-Hosini; Morsy, Tosson A

    2014-08-01

    Insecticides are used to control diseases spread by arthropods, but theys vary greatly in toxicity. Toxicity depends on the chemical and physical properties of a substance, and may be defined as the quality of being poisonous or harmful to animals or plants. Poisons have many different modes of action, but in general cause biochemical changes which interfere with normal body functions. Toxicity can be either acute or chronic. Acute toxicity is the ability of a substance to cause harmful effects which develop rapidly following absorption, i.e. a few hours or a day. Chronic toxicity is the ability of a substance to cause adverse health effects resulting from long-term exposure to a substance. There is a great range in the toxicity of insecticides to humans. The relative hazard of an insecticide is dependent upon the toxicity of the pesticide, the dose received and the length of time exposed. A hazard can be defined as a source of danger. The great majority of insecticides are poisonous to man and his beneficial insects and animals and are carcinogenic agents particularly, the halogenated hydrocarbons containing benzene ring.

  3. Integrating Human Factors into Space Vehicle Processing for Risk Management

    Science.gov (United States)

    Woodbury, Sarah; Richards, Kimberly J.

    2008-01-01

    This presentation will discuss the multiple projects performed in United Space Alliance's Human Engineering Modeling and Performance (HEMAP) Lab, improvements that resulted from analysis, and the future applications of the HEMAP Lab for risk assessment by evaluating human/machine interaction and ergonomic designs.

  4. An IARC Manual series aimed at assisting cancer epidemiology and prevention. "Environmental carcinogens: selected methods of analysis".

    Science.gov (United States)

    O'Neill, I K; Fishbein, L

    1986-01-01

    Since 1975, the IARC has been preparing a series of volumes entitled "Environmental Carcinogens: Selected Methods of Analysis" (IARC Manual series) of which the purposes are to assist analysts, epidemiologists and regulatory authorities in planning or performing exposure measurements that are truly comparable between different studies. The Manual series provides expert information within each volume on multi-media sampling, methods of analyses and some background of epidemiology, metabolism, use/occurrence for a group of known or suspect carcinogens. So far, eleven volumes have been published or are in preparation on the following subjects: N-nitrosamines, vinyl chloride, PAH, aromatic amines, mycotoxins, N-nitroso compounds, volatile halogenated hydrocarbons, metals, passive smoking, benzene and alkylated benzenes, dioxins, PCDFs and PCBs. The presentation will discuss needs and priorities for use of analytical chemistry in estimating exposures of apparently greatest relevance to cancer causation, i.e. the approach to developing this series. Indications from epidemiology, evaluations of carcinogenic risk to humans, and recent developments in total exposure assessment are that new methods and matrices need more emphasis, e.g. as with biochemical dosimetry, exhaled breath, and in indoor air.

  5. A Reexamination of the PPAR-α Activation Mode of Action as a Basis for Assessing Human Cancer Risks of Environmental Contaminants

    Science.gov (United States)

    Guyton, Kathryn Z.; Chiu, Weihsueh A.; Bateson, Thomas F.; Jinot, Jennifer; Scott, Cheryl Siegel; Brown, Rebecca C.; Caldwell, Jane C.

    2009-01-01

    Background Diverse environmental contaminants, including the plasticizer di(2-ethylhexyl)phthalate (DEHP), are hepatocarcinogenic peroxisome proliferators in rodents. Peroxisome proliferator–activated receptor-α (PPAR-α) activation and its sequelae have been proposed to constitute a mode of action (MOA) for hepatocarcinogenesis by such agents as a sole causative factor. Further, based on a hypothesized lower sensitivity of humans to this MOA, prior reviews have concluded that rodent hepatocarcinogenesis by PPAR-α agonists is irrelevant to human carcinogenic risk. Data synthesis Herein, we review recent studies that experimentally challenge the PPAR-α activation MOA hypothesis, providing evidence that DEHP is hepatocarcinogenic in PPAR-α–null mice and that the MOA but not hepatocarcinogenesis is evoked by PPAR-α activation in a transgenic mouse model. We further examine whether relative potency for PPAR-α activation or other steps in the MOA correlates with tumorigenic potency. In addition, for most PPAR-α agonists of environmental concern, available data are insufficient to characterize relative human sensitivity to this rodent MOA or to induction of hepatocarcinogenesis. Conclusions Our review and analyses raise questions about the hypothesized PPAR-α activation MOA as a sole explanation for rodent hepatocarcinogenesis by PPAR-α agonists and therefore its utility as a primary basis for assessing human carcinogenic risk from the diverse compounds that activate PPAR-α. These findings have broad implications for how MOA hypotheses are developed, tested, and applied in human health risk assessment. We discuss alternatives to the current approaches to these key aspects of mechanistic data evaluation. PMID:20049115

  6. Analysis of human papillomavirus 16 variants and risk for cervical cancer in Chinese population.

    Science.gov (United States)

    Hang, Dong; Yin, Yin; Han, Jing; Jiang, Jie; Ma, Hongxqia; Xie, Shuanghua; Feng, Xiaoshuang; Zhang, Kai; Hu, Zhibin; Shen, Hongbing; Clifford, Gary M; Dai, Min; Li, Ni

    2016-01-15

    HPV16 is the most carcinogenic HPV type, but only a minority of HPV16 infections progress to cancer. Intratype genetic variants of HPV16 have been suggested to confer differential carcinogenicity. To investigate risk implications of HPV16 variants among Chinese women, a case-control study was conducted with 298 cervical cancer patients and 85 controls (all HPV16-positive). HPV16 isolates were predominantly of the A variant lineage, and variants of A4 (previously named "Asian") sublineage were common. A4/Asian variants were significantly associated with increased risk of cervical cancer compared to A1-3 (OR=1.72, 95% CI=1.04-2.85). Furthermore, a meta-analysis including 703 cases and 323 controls from East Asia confirmed the association (OR=2.82, 95% CI=1.44-5.52). In conclusion, A4 variants appear to predict higher risk of cervical cancer among HPV16-positive women, which may provide clues to the genetic basis of differences in the carcinogenicity of HPV16 variants.

  7. Dietary acrylamide intake and brain cancer risk

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Background: Acrylamide is a probable human carcinogen, which is present in several heat-treatedfood s. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon acrylamid

  8. Dietary acrylamide intake and brain cancer risk

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Background: Acrylamide is a probable human carcinogen, which is present in several heat-treatedfood s. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon

  9. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  10. Long-term environmental monitoring of persistent organic pollutants and metals in a chemical/petrochemical area: Human health risks

    Energy Technology Data Exchange (ETDEWEB)

    Nadal, Marti [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenc 21, 43201 Reus, Catalonia (Spain); Schuhmacher, Marta [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenc 21, 43201 Reus, Catalonia (Spain); Environmental Engineering Laboratory, Departament d' Enginyeria Quimica, Universitat Rovira i Virgili, Av. Paisos Catalans 26, 43007 Tarragona, Catalonia (Spain); Domingo, Jose L., E-mail: joseluis.domingo@urv.cat [Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Sant Llorenc 21, 43201 Reus, Catalonia (Spain)

    2011-07-15

    Organic pollutants such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polychlorinated naphthalenes (PCNs) and polycyclic aromatic hydrocarbons (PAHs), as well as some metals are periodically monitored in soil and vegetation samples collected in Tarragona County (Spain). We here report the temporal trends of the concentrations of the above pollutants between the initial survey (2002) and that recently (2009) performed. The area under evaluation was divided into 4 sections (chemical, petrochemical, urban/residential and unpolluted). In general terms, urban soils presented the highest concentrations of PCDD/Fs, PCNs and PAHs, confirming that traffic is a very important emission source of these pollutants. In addition, substantially higher levels of PAHs and some metals were found in vegetation samples from the petrochemical complex. The assessment of health risks of these contaminants indicated that the current concentrations of micropollutants did not mean additional non-carcinogenic or cancer risks for the population living in the zone. - Highlights: > Traffic is an important emission source of persistent organic pollutants. > Oil refineries could be notable releasers of PAHs and some metals in the area. > Soil pollutant levels are notably lower than threshold values. > The air quality of Tarragona area is not greatly affected by metals and POPs. > The current exposure to micropollutants does not mean additional health risks. - Human exposure to environmental micropollutants in the industrial area of Tarragona does not mean additional health risks.

  11. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza-Figueroa, T.; Lopez-Revilla, R.; Villa-Trevino, S.

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with (/sup 3/H) dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: 1) the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and 2) the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340..mu..M) and to the precarcinogens benzo(a)pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  12. Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures.

    Science.gov (United States)

    Mendoza-Figueroa, T; López-Revilla, R; Villa-Treviño, S

    1985-01-01

    The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with [3H] dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1 mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340 microM) and to the precarcinogens benzo[a]pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.

  13. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.;

    1996-01-01

    A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...

  14. Biomonitoring human exposure to environmental carcinogenic chemicals

    NARCIS (Netherlands)

    Farmer, P.B.; Sepai, O.; Lawrence, R.; Autrup, H.; Nielsen, P.S.; Baan, R.A.; Delft, J.H.M. van; Steenwinkel, M.J.S.T.; et al.

    1996-01-01

    A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of secondary biological

  15. Monitoring human exposure to 2-hydroxyethylating carcinogens

    DEFF Research Database (Denmark)

    Farmer, P.B.; Cordero, Rosa; Autrup, Herman

    1996-01-01

    agents was also studied by the analysis of umbilical cord hemoglobin. The adduct levels in smokers were significantly higher than those in nonsmokers. The adduct levels in umbilical cord blood globin were quantitatively related to those in maternal blood (maternal:fetal ratio 2.7 in smokers and 2...

  16. Risk Factors for Anal HPV Infection and Anal Precancer in HIV-Infected Men Who Have Sex With Men

    OpenAIRE

    Schwartz, Lauren M.; Castle, Philip E.; Follansbee, Stephen; Borgonovo, Sylvia; Fetterman, Barbara; Tokugawa, Diane; Lorey, Thomas S.; Sahasrabuddhe, Vikrant V.; Luhn, Patricia; Gage, Julia C; Darragh, Teresa M.; Wentzensen, Nicolas

    2013-01-01

    Background. Carcinogenic human papillomaviruses (HPVs) cause a large proportion of anal cancers. Human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) are at increased risk of HPV infection and anal cancer compared with HIV-negative men. We evaluated risk factors for HPV infection and anal precancer in a population of HIV-infected MSM.

  17. Human risk from thermotolerant Campylobacter on broiler meat in Denmark

    DEFF Research Database (Denmark)

    Boysen, Louise; Nauta, Maarten; Ribeiro Duarte, Ana Sofia

    2013-01-01

    This paper describes a new approach by which changes over time in the relative risk of human campylobacteriosis from broiler meat are evaluated through quantitative microbiological risk assessment modelling. Danish surveillance data collected at retail from 2001 to 2010 on numbers of thermotolerant...... providing the most relevant outcome for food safety risk managers....... Campylobacter spp. on Danish produced and imported chilled and frozen broiler meat were the basis for the investigation. The aim was to explore if the risk from the different meat categories had changed over time as a consequence of implemented intervention strategies. The results showed a slight decrease from...

  18. Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

    Science.gov (United States)

    Harada, Takanori; Takeda, Makio; Kojima, Sayuri; Tomiyama, Naruto

    2016-01-01

    Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p′-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT. PMID:26977256

  19. Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

    Science.gov (United States)

    de Barros, F.; Rubin, Y.; Maxwell, R. M.

    2013-12-01

    In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose

  20. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

    Science.gov (United States)

    Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

    2014-04-01

    Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health.

  1. Predicting risk sensitivity in humans and lower animals: risk as variance or coefficient of variation.

    Science.gov (United States)

    Weber, Elke U; Shafir, Sharoni; Blais, Ann-Renee

    2004-04-01

    This article examines the statistical determinants of risk preference. In a meta-analysis of animal risk preference (foraging birds and insects), the coefficient of variation (CV), a measure of risk per unit of return, predicts choices far better than outcome variance, the risk measure of normative models. In a meta-analysis of human risk preference, the superiority of the CV over variance in predicting risk taking is not as strong. Two experiments show that people's risk sensitivity becomes strongly proportional to the CV when they learn about choice alternatives like other animals, by experiential sampling over time. Experience-based choices differ from choices when outcomes and probabilities are numerically described. Zipf's law as an ecological regularity and Weber's law as a psychological regularity may give rise to the CV as a measure of risk.

  2. 78 FR 67371 - Draft Report on Carcinogens Monographs for ortho-Toluidine and Pentachlorophenol and By-products...

    Science.gov (United States)

    2013-11-12

    ... HUMAN SERVICES National Institutes of Health Draft Report on Carcinogens Monographs for ortho-Toluidine... Report on Carcinogens (RoC) Monographs for ortho-Toluidine and Pentachlorophenol and By-products of its... a.m. until adjournment, approximately 11:30 a.m. Document Availability: Draft monographs...

  3. 78 FR 51733 - Draft Report on Carcinogens Monographs for ortho-Toluidine and Pentachlorophenol and By-Products...

    Science.gov (United States)

    2013-08-21

    ... HUMAN SERVICES National Institutes of Health Draft Report on Carcinogens Monographs for ortho-Toluidine... Carcinogens (RoC) Monographs for ortho-Toluidine and Pentachlorophenol and By-products of its Synthesis.... Document Availability: Draft monographs will be available by August 28, 2013, at...

  4. Arsenic biogeochemistry and human health risk assessment in organo-arsenical pesticide-applied acidic and alkaline soils: an incubation study.

    Science.gov (United States)

    Datta, Rupali; Sarkar, Dibyendu; Sharma, Saurabh; Sand, Kumarswamy

    2006-12-15

    Organo-arsenical compounds are considered non-carcinogenic, and hence, are still allowed by the regulatory agencies for use in agriculture as pesticides. Due to rapid encroachment of suburban areas into former agricultural lands, the potential for human exposure to soil-arsenic has increased tremendously in recent years. However, insufficient data is available on the stability of organo-arsenicals in soils; as to whether they remain in an organic form, or are converted over time to potentially carcinogenic inorganic forms. A static incubation study was conducted to estimate soil speciation and in-vitro bioavailability (i.e., bioaccessibility) of arsenic as a function of soil properties. Two chemically variant soil types were chosen, based on their potential differences with respect to arsenic reactivity: an acid sand with minimal arsenic retention capacity and an alkaline clay loam with relatively high concentrations of Fe/Al and Ca/Mg. The soils were amended with dimethylarsenic acid (DMA) at three rates, 45, 225 and 450 mg/kg, and incubated for 1 year. A sequential extraction scheme was employed to identify the geochemical forms of arsenic in soils, which were correlated with the in-vitro bioavailable fractions of arsenic. Human health risk calculated in terms of excess cancer risk (ECR) showed that risk assessment based on bioaccessible arsenic concentrations instead of the traditional total soil arsenic is a more realistic approach. Results showed that soil properties (such as pH, Fe/Al content and soil texture) of the two soils dictated the geochemical speciation, and hence, bioaccessibility of arsenic from DMA, indicating that the use of organic arsenicals as pesticides in mineral soils may not be a safe practice from a human health risk perspective.

  5. Risks of Mycotoxins from Mycoinsecticides to Humans.

    Science.gov (United States)

    Hu, Qiongbo; Li, Fuxia; Zhang, Yuping

    2016-01-01

    There are more than thirty mycotoxins produced by fungal entomopathogens. Totally, they belong to two classes, NRP and PK mycotoxins. Most of mycotoxins have not been paid sufficient attention yet. Generally, mycotoxins do not exist in mycoinsecticide and might not be released to environments unless entomogenous fungus proliferates and produces mycotoxins in host insects or probably in plants. Some mycotoxins, destruxins as an example, are decomposed in host insects before they, with the insect's cadavers together, are released to environments. Many species of fungal entomopathogens have the endophytic characteristics. But we do not know if fungal entomopathogens produce mycotoxins in plants and release them to environments. On the contrary, the same mycotoxins produced by phytopathogens such as Fusarium spp. and Aspergillus spp. have been paid enough concerns. In conclusion, mycotoxins from mycoinsecticides have limited ways to enter environments. The risks of mycotoxins from mycoinsecticides contaminating foods are controllable.

  6. Risks of Mycotoxins from Mycoinsecticides to Humans

    Science.gov (United States)

    Hu, Qiongbo; Li, Fuxia; Zhang, Yuping

    2016-01-01

    There are more than thirty mycotoxins produced by fungal entomopathogens. Totally, they belong to two classes, NRP and PK mycotoxins. Most of mycotoxins have not been paid sufficient attention yet. Generally, mycotoxins do not exist in mycoinsecticide and might not be released to environments unless entomogenous fungus proliferates and produces mycotoxins in host insects or probably in plants. Some mycotoxins, destruxins as an example, are decomposed in host insects before they, with the insect's cadavers together, are released to environments. Many species of fungal entomopathogens have the endophytic characteristics. But we do not know if fungal entomopathogens produce mycotoxins in plants and release them to environments. On the contrary, the same mycotoxins produced by phytopathogens such as Fusarium spp. and Aspergillus spp. have been paid enough concerns. In conclusion, mycotoxins from mycoinsecticides have limited ways to enter environments. The risks of mycotoxins from mycoinsecticides contaminating foods are controllable. PMID:27144161

  7. Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

    Directory of Open Access Journals (Sweden)

    Budnik Lygia T

    2012-01-01

    Full Text Available Abstract Background Although ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage. The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity. Methods We performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis. Results Out of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49, P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage. Conclusions Both the epidemiological evidence and toxicological data suggest a possible link between methyl

  8. Regulatory Forum commentary: alternative mouse models for future cancer risk assessment.

    Science.gov (United States)

    Morton, Daniel; Sistare, Frank D; Nambiar, Prashant R; Turner, Oliver C; Radi, Zaher; Bower, Nancy

    2014-07-01

    International regulatory and pharmaceutical industry scientists are discussing revision of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight-of-evidence approach is proposed to determine the need for rodent carcinogenicity studies. For compounds with high human cancer risk, the product may be labeled appropriately without conducting rodent carcinogenicity studies. For compounds with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity testing may add significant value to cancer risk assessment, a 2-year rat study and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In many cases, therefore, one rodent carcinogenicity study could be sufficient. The rasH2 model predicts neoplastic findings relevant to human cancer risk assessment as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes, and often will be preferable to a 2-year rodent study. Before revising ICH S1 guidance, a prospective evaluation will be conducted to test the proposed weight-of-evidence approach. This evaluation offers an opportunity for a secondary analysis comparing the value of alternative mouse models and 2-year rodent studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk assessment.

  9. Comparative view on risk factor of human death

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Atsuhiko; Sugahara, Tsutomu [Health Research Foundation, Kyoto (Japan)

    1999-09-01

    Human being, namely. 'living' get involved in risk factor. Even if risk is limited to lethal danger, human history is coresponding with numberless risks from ancient up to today. For example, there is increase in risk of death by car-crash owing to get high efficiency in transfer. In Japan, the death toll by car-accident is about ten thousands per year constantly. State of deaths by car-accident not only include driver itself but cyclist and pedestrian. Death rate of both the cyclist and pedestrian amounts to 40% of all. In the age, rate of fracture as result of fall-down while walking is very high. It shows that the aged who give up driving and get out of danger car-crush are attacked the another accident as walkers. On type of danger, the decrease in risk of one-side come to increase in risk of other side. That is 'risk trade-off'. Examples of risk trade-off as above are numerous in environment. Acceptable death rate of various causes is about 10{sup -4} per year in generally. Flight accident happens on rare occasions (10{sup -7} per year in Japan, usually). Spite of insignificant probability, people fear by both reasons that the possibility of rescue is very few and the size of accident is enormous. In the cases of flight and nuclear power plant, estimated accidents is sever, but its probability is very small. Therefore, risk of annual deaths by accident must be considered as multiplication of size of risk (deaths per year) by probability (frequency per year). Obtained result by such analysis shall conduct to right risk perception and stable 'risk acceptance'. (author)

  10. A 21st century roadmap for human health risk assessment.

    Science.gov (United States)

    Pastoor, Timothy P; Bachman, Ammie N; Bell, David R; Cohen, Samuel M; Dellarco, Michael; Dewhurst, Ian C; Doe, John E; Doerrer, Nancy G; Embry, Michelle R; Hines, Ronald N; Moretto, Angelo; Phillips, Richard D; Rowlands, J Craig; Tanir, Jennifer Y; Wolf, Douglas C; Boobis, Alan R

    2014-08-01

    The Health and Environmental Sciences Institute (HESI)-coordinated Risk Assessment in the 21st Century (RISK21) project was initiated to develop a scientific, transparent, and efficient approach to the evolving world of human health risk assessment, and involved over 120 participants from 12 countries, 15 government institutions, 20 universities, 2 non-governmental organizations, and 12 corporations. This paper provides a brief overview of the tiered RISK21 framework called the roadmap and risk visualization matrix, and articulates the core principles derived by RISK21 participants that guided its development. Subsequent papers describe the roadmap and matrix in greater detail. RISK21 principles include focusing on problem formulation, utilizing existing information, starting with exposure assessment (rather than toxicity), and using a tiered process for data development. Bringing estimates of exposure and toxicity together on a two-dimensional matrix provides a clear rendition of human safety and risk. The value of the roadmap is its capacity to chronicle the stepwise acquisition of scientific information and display it in a clear and concise fashion. Furthermore, the tiered approach and transparent display of information will contribute to greater efficiencies by calling for data only as needed (enough precision to make a decision), thus conserving animals and other resources.

  11. Industrial metal pollution in water and probabilistic assessment of human health risk.

    Science.gov (United States)

    Saha, Narottam; Rahman, M Safiur; Ahmed, Mohammad Boshir; Zhou, John L; Ngo, Huu Hao; Guo, Wenshan

    2016-10-28

    Concentration of eight heavy metals in surface and groundwater around Dhaka Export Processing Zone (DEPZ) industrial area were investigated, and the health risk posed to local children and adult residents via ingestion and dermal contact was evaluated using deterministic and probabilistic approaches. Metal concentrations (except Cu, Mn, Ni, and Zn) in Bangshi River water were above the drinking water quality guidelines, while in groundwater were less than the recommended limits. Concentration of metals in surface water decreased as a function of distance. Estimations of non-carcinogenic health risk for surface water revealed that mean hazard index (HI) values of As, Cr, Cu, and Pb for combined pathways (i.e., ingestion and dermal contact) were >1.0 for both age groups. The estimated risk mainly came from the ingestion pathway. However, the HI values for all the examined metals in groundwater were probabilistically estimated 95th percentile values of TCR exceeded the benchmark, mean TCR values were less than 1 × 10(-4). Simulated results showed that 20.13% and 5.43% values of TCR for surface water were >1 × 10(-4) for adult and children, respectively. Deterministic and probabilistic estimations of cancer risk through exposure to groundwater were well below the safety limit. Overall, the population exposed to Bangshi River water remained at carcinogenic and non-carcinogenic health threat and the risk was higher for adults. Sensitivity analysis identified exposure duration (ED) and ingestion rate (IR) of water as the most relevant variables affecting the probabilistic risk estimation model outcome.

  12. TANK S-109 LONG TERM HUMAN HEALTH RISK CALCULATIONS

    Energy Technology Data Exchange (ETDEWEB)

    CARLSON, S.E.

    2003-12-16

    This document provides Tank S-109 long-term human risks calculations, in support of Functions and Requirements document (RPP-18812) as required by milestone M-45-00 of the Hanford Federal Facility Agreement and Consent Order. This calculation was performed to provide a screening-level assessment of long-term human health risk associated with potential leakage that could occur during waste retrieval operations for tank S-109 This calculation supports the development of tank S-109 waste retrieval functions and requirements as documented in RPP-18812. Risks associated with current waste and potential residual waste in tank S-109, as well as risk associated with other S farm tanks, were not of interest and were not evaluated.

  13. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen?

    Science.gov (United States)

    Surh, Y J; Lee, S S

    1996-03-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent ingredient of the Capsicum fruits such as hot green and red peppers. Besides its use as a food additive in various spicy cuisines, capsaicin is currently utilized for therapeutic purposes to treat various peripheral painful conditions such as rheumatoid arthritis and diabetic neuropathy. Considering consumption of capsaicin as a food additive and its current medicinal application in humans, correct evaluation and precise assessment of any harmful effects of this compound are essential from the public health standpoint. Numerous investigations have been conducted to determine the potential mutagenic and carcinogenic activity of capsaicin and chili pepper, but results are discordant. This review briefly examines findings in the literature of studies testing mutagenicity and tumorigenicity of capsaicin and presents a possible mechanistic basis for the dual effects exerted by the compound.

  14. Human monitoring of phthalates and risk assessment.

    Science.gov (United States)

    Koo, Hyun Jung; Lee, Byung Mu

    2005-08-27

    Some phthalates, such as di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), and their metabolites are suspected of producing teratogenic and endocrino-disrupting effects. In this study, urinary levels of phthalates (DEHP, DBP, diethyl phthalate (DEP), butylbenzyl phthalate BBP), and monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) were measured by high performance liquid chromatography (HPLC) in human populations (women [hospital visitors], n = 150, and children, n = 150). Daily exposure level of DEHP in children was estimated to be 12.4 microg/kg body weight/d (male 9.9 microg/kg body weight/d, female 17.8 microg/kg body weight/d), but, in women was estimated to be 41.7 microg/kg body weight/d, which exceeded the tolerable daily intake (TDI, 37 microg/kg body weight/day) level established by the European Union (EU) Scientific Committee for Toxicity, Ecotoxicity, and the Environment (SCTEE) based on reproductive toxicity. Based on these data, hazard indices (HIs) were calculated to be 1.12 (41.7/37 TDI) for women and 0.33 (12.4/37 TDI) for children, respectively. These data suggest that Koreans (women and children) were exposed to significant levels of phthalates, which should be reduced to as low a level as technologically feasible to protect Koreans from the exposure to toxic phthalates.

  15. Nanotechnology and human health: risks and benefits.

    Science.gov (United States)

    Cattaneo, Anna Giulia; Gornati, Rosalba; Sabbioni, Enrico; Chiriva-Internati, Maurizio; Cobos, Everardo; Jenkins, Marjorie R; Bernardini, Giovanni

    2010-11-01

    Nanotechnology is expected to be promising in many fields of medical applications, mainly in cancer treatment. While a large number of very attractive exploitations open up for the clinics, regulatory agencies are very careful in admitting new nanomaterials for human use because of their potential toxicity. The very active research on new nanomaterials that are potentially useful in medicine has not been counterbalanced by an adequate knowledge of their pharmacokinetics and toxicity. The different nanocarriers used to transport and release the active molecules to the target tissues should be treated as additives, with potential side effects of themselves or by virtue of their dissolution or aggregation inside the body. Only recently has a systematic classification of nanomaterials been proposed, posing the basis for dedicated modeling at the nanoscale level. The use of in silico methods, such as nano-QSAR and PSAR, while highly desirable to expedite and rationalize the following stages of toxicological research, are not an alternative, but an introduction to mandatory experimental work.

  16. Human health risk assessment of chloroxylenol in liquid hand soap and dishwashing soap used by consumers and health-care professionals.

    Science.gov (United States)

    Yost, Lisa J; Rodricks, Joseph D; Turnbull, Duncan; DeLeo, Paul C; Nash, J Frank; Quiñones-Rivera, Antonio; Carlson, Pete A

    2016-10-01

    A quantitative human risk assessment of chloroxylenol was conducted for liquid hand and dishwashing soap products used by consumers and health-care workers. The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity. No observed adverse effect levels (NOAEL) were established from chronic toxicity studies, specifically a carcinogenicity study that found no cancer excess (18 mg/kg-day) and studies of developmental and reproductive toxicity (100 mg/kg-day). Exposure to chloroxylenol for adults and children was estimated for two types of rinse-off cleaning products, one liquid hand soap, and two dishwashing products. The identified NOAELs were used together with exposure estimates to derive margin of exposure (MOE) estimates for chloroxylenol (i.e., estimates of exposure over NOAELs). These estimates were designed with conservative assumptions and likely overestimate exposure and risk (i.e., highest frequency, 100% dermal penetration). The resulting MOEs ranged from 178 to over 100, 000, 000 indicating negligibly small potential for harm related to consumer or health-care worker exposure to chloroxylenol in liquid soaps used in dish washing and hand washing. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

    Science.gov (United States)

    2000-01-01

    On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated.

  18. Concentrations of environmental organic contaminants in meat and meat products and human dietary exposure: A review.

    Science.gov (United States)

    Domingo, José L

    2017-09-01

    Meat and meat products is one of the most relevant food groups in an important number of human diets. Recently, the IARC, based on results of a number of epidemiological studies, classified the consumptions of red meat and processed meat as "probably carcinogenic to humans" and as "carcinogenic to humans", respectively. It was suggested that the substances responsible of the potential carcinogenicity would be mainly generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures. However, the exposure to environmental pollutants through meat consumption was not discussed. The purpose of the present paper was to review recent studies reporting the concentrations of PCDD/Fs, DL-PCBs and PAHs in meat and meat products, as well as the human exposure to these pollutants through the diet. It is concluded that the health risks derived from exposure to carcinogenic environmental contaminants must be considered in the context of each specific diet, which besides meat and meat products, includes other foodstuffs containing also chemical pollutants, some of them with carcinogenic potential. Anyhow, meat and meat products are not the main food group responsible of the dietary exposure to carcinogenic (or probably carcinogenic) environmental organic pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid......-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  20. Assessment of Industry-Induced Urban Human Health Risks Related to Benzo[a]pyrene based on a Multimedia Fugacity Model: Case Study of Nanjing, China

    Directory of Open Access Journals (Sweden)

    Linyu Xu

    2015-05-01

    Full Text Available Large amounts of organic pollutants emitted from industries have accumulated and caused serious human health risks, especially in urban areas with rapid industrialization. This paper focused on the carcinogen benzo[a]pyrene (BaP from industrial effluent and gaseous emissions, and established a multi-pathway exposure model based on a Level IV multimedia fugacity model to analyze the human health risks in a city that has undergone rapid industrialization. In this study, GIS tools combined with land-use data was introduced to analyze smaller spatial scales so as to enhance the spatial resolution of the results. An uncertainty analysis using a Monte Carlo simulation was also conducted to illustrate the rationale of the probabilistic assessment mode rather than deterministic assessment. Finally, the results of the case study in Nanjing, China indicated the annual average human cancer risk induced by local industrial emissions during 2002–2008 (lowest at 1.99´10–6 in 2008 and highest at 3.34´10–6 in 2004, which was lower than the USEPA prescriptive level (1´10–6–1´10–4 but cannot be neglected in the long term. The study results could not only instruct the BaP health risk management but also help future health risk prediction and control.

  1. Assessment of Industry-Induced Urban Human Health Risks Related to Benzo[a]pyrenebased on a Multimedia Fugacity Model: Case Study of Nanjing, China.

    Science.gov (United States)

    Xu, Linyu; Song, Huimin; Wang, Yan; Yin, Hao

    2015-05-29

    Large amounts of organic pollutants emitted from industries have accumulated and caused serious human health risks, especially in urban areas with rapid industrialization. This paper focused on the carcinogen benzo[a]pyrene (BaP) from industrial effluent and gaseous emissions, and established a multi-pathway exposure model based on a Level IV multimedia fugacity model to analyze the human health risks in a city that has undergone rapid industrialization. In this study, GIS tools combined with land-use data was introduced to analyze smaller spatial scales so as to enhance the spatial resolution of the results. An uncertainty analysis using a Monte Carlo simulation was also conducted to illustrate the rationale of the probabilistic assessment mode rather than deterministic assessment. Finally, the results of the case study in Nanjing, China indicated the annual average human cancer risk induced by local industrial emissions during 2002-2008 (lowest at 1.99x10(-6) in 2008 and highest at 3.34x10(-6) in 2004), which was lower than the USEPA prescriptive level (1x10(-6)-1x10(-4)) but cannot be neglected in the long term. The study results could not only instruct the BaP health risk management but also help future health risk prediction and control.

  2. Defining Human Failure Events for Petroleum Risk Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ronald L. Boring; Knut Øien

    2014-06-01

    In this paper, an identification and description of barriers and human failure events (HFEs) for human reliability analysis (HRA) is performed. The barriers, called target systems, are identified from risk significant accident scenarios represented as defined situations of hazard and accident (DSHAs). This report serves as the foundation for further work to develop petroleum HFEs compatible with the SPAR-H method and intended for reuse in future HRAs.

  3. Dietary Cadmium Intake and Risk of Breast, Endometrial and Ovarian Cancer in Danish Postmenopausal Women: A Prospective Cohort Study

    OpenAIRE

    2014-01-01

    Purpose Cadmium is a human lung carcinogen and possesses estrogen-like activity. This combination of carcinogenic and estrogenic activity makes cadmium a contaminant of high concern for hormone-related cancers. Diet and smoking are the main sources of cadmium exposure. The aim of this study was to investigate the association between dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal woman. Methods We estimated dietary cadmium intake in the Diet,...

  4. Benefits and risks of fish consumption for the human health

    Directory of Open Access Journals (Sweden)

    Ana Carolina Fernandes

    2012-04-01

    Full Text Available The article aimed at identifying and discussing scientific evidences on the benefits and risks of fish consumption the human health. There was a systematic survey for articles published from 2003 and May 2011, at the MedLine, Scopus, SciELO, Lilacs and Google Scholar databases. The key words used were: fish, food intake, omega-3 fatty acids, fatty fish, benefits, risk, and consumption. The search produced 12,632 articles, 25 eligible cohort studies on possible benefits, 61 on risks and 10 studies that assessed the "risk/benefit" relation. Of the 25 works, 14 suggested a preventive effect of fish consumption related to cardiovascular diseases, depression, cataract and some types of cancer. Evidences of a relation between exposure to mercury and an increase in the risk of neurological disorders, but not of cardiovascular diseases, were also found. Given the importance of fish consumption, its possible risks and the lack of Brazilian studies on the topic, it is important to conduct more longitudinal studies that assess both the benefits and risks of fish consumption for the human health. We also emphasize the need for policies to reduce exposure of fish and seafood to mercury and other contaminants.

  5. Metabolic state alters economic decision making under risk in humans.

    Directory of Open Access Journals (Sweden)

    Mkael Symmonds

    Full Text Available BACKGROUND: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores. Specifically, animals often express a preference for risky (more variable food sources when below a metabolic reference point (hungry, and safe (less variable food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. METHODOLOGY/PRINCIPAL FINDINGS: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake, and circulating leptin levels (providing an assay of energy reserves. We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. CONCLUSIONS/SIGNIFICANCE: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that

  6. Statistical aspects and risks of human-caused earthquakes

    Science.gov (United States)

    Klose, C. D.

    2013-12-01

    The seismological community invests ample human capital and financial resources to research and predict risks associated with earthquakes. Industries such as the insurance and re-insurance sector are equally interested in using probabilistic risk models developed by the scientific community to transfer risks. These models are used to predict expected losses due to naturally occurring earthquakes. But what about the risks associated with human-caused earthquakes? Such risk models are largely absent from both industry and academic discourse. In countries around the world, informed citizens are becoming increasingly aware and concerned that this economic bias is not sustainable for long-term economic growth, environmental and human security. Ultimately, citizens look to their government officials to hold industry accountable. In the Netherlands, for example, the hydrocarbon industry is held accountable for causing earthquakes near Groningen. In Switzerland, geothermal power plants were shut down or suspended because they caused earthquakes in canton Basel and St. Gallen. The public and the private non-extractive industry needs access to information about earthquake risks in connection with sub/urban geoengineeing activities, including natural gas production through fracking, geothermal energy production, carbon sequestration, mining and water irrigation. This presentation illuminates statistical aspects of human-caused earthquakes with respect to different geologic environments. Statistical findings are based on the first catalog of human-caused earthquakes (in Klose 2013). Findings are discussed which include the odds to die during a medium-size earthquake that is set off by geomechanical pollution. Any kind of geoengineering activity causes this type of pollution and increases the likelihood of triggering nearby faults to rupture.

  7. A review of biosensing techniques for detection of trace carcinogen contamination in food products.

    Science.gov (United States)

    Li, Zhanming; Yu, Yue; Li, Zhiliang; Wu, Tao

    2015-04-01

    Carcinogen contaminations in the food chain, for example heavy metal ions, pesticides, acrylamide, and mycotoxins, have caused serious health problems. A major objective of food-safety research is the identification and prevention of exposure to these carcinogens, because of their impossible-to-reverse tumorigenic effects. However, carcinogen detection is difficult because of their trace-level presence in food. Thus, reliable and accurate separation and determination methods are essential to protect food safety and human health. This paper summarizes the state of the art in separation and determination methods for analyzing carcinogen contamination, especially the advances in biosensing methods. Furthermore, the application of promising technology including nanomaterials, imprinted polymers, and microdevices is detailed. Challenges and perspectives are also discussed.

  8. Workplace carcinogen and pesticide exposures in Costa Rica.

    Science.gov (United States)

    Partanen, Timo; Chaves, Jorge; Wesseling, Catharina; Chaverri, Fabio; Monge, Patricia; Ruepert, Clemens; Aragón, Aurora; Kogevinas, Manolis; Hogstedt, Christer; Kauppinen, Timo

    2003-01-01

    The CAREX data system converts national workforce volumes and proportions of workers exposed to workplace carcinogens into numbers of exposed in 55 industrial categories. CAREX was adapted for Costa Rica for 27 carcinogens and seven groups of pesticides. Widespread workplace carcinogens in the 1.3 million workforce of Costa Rica are solar radiation (333,000 workers), diesel engine exhaust (278,000), environmental tobacco smoke (71,000), hexavalent chromium compounds (55,000), benzene (52,000), wood dust (32,000), silica dust (27,000), lead and inorganic lead compounds (19,000), and polycyclic aromatic compounds (17,000). The most ubiquitous pesticides were paraquat and diquat (175,000), mancozeb, maneb, and zineb (49,000), chlorothalonil (38,000), benomyl (19,000), and chlorophenoxy herbicides (11,000). Among women, formaldehyde, radon, and methylene chloride overrode pesticides, chromium, wood dust, and silica dust in numbers of exposed. High-risk sectors included agriculture, construction, personal and household services, land and water transport and allied services, pottery and similar industries, woodworks, mining, forestry and logging, fishing, manufacturing of electrical machinery, and bar and restaurant personnel.

  9. Countries at Risk: Heightened Human Security Risk to States With Transboundary Water Resources and Instability

    Science.gov (United States)

    Veilleux, J. C.; Sullivan, G. S.; Paola, C.; Starget, A.; Watson, J. E.; Hwang, Y. J.; Picucci, J. A.; Choi, C. S.

    2014-12-01

    The Countries at Risk project is a global assessment of countries with transboundary water resources that are at risk for conflict because of high human security instability. Building upon Basins at Risk (BAR) research, our team used updated Transboundary Freshwater Dispute Database georeferenced social and environmental data, quantitative data from global indices, and qualitative data from news media sources. Our assessment considered a combination of analyzing 15 global indices related to water or human security to identify which countries scored as highest risk in each index. From this information, we were able to assess the highest risk countries' human security risk by using a new human security measurement tool, as well as comparing this analysis to the World Bank's Fragile States Index and the experimental Human Security Index. In addition, we identified which countries have the highest number of shared basins, the highest percentage of territory covered by a transboundary basin, and the highest dependency of withdrawal from transboundary waters from outside their country boundaries. By synthesizing these social and environmental data assessments, we identified five countries to analyze as case studies. These five countries are Afghanistan, China, Iraq, Moldova, and Sudan. We created a series of 30 maps to spatial analyze the relationship between the transboundary basins and social and environmental parameters to include population, institutional capacity, and physical geography by country. Finally, we synthesized our spatial analysis, Human Security Key scores, and current events scored by using the BAR scale to determine what aspects and which basins are most at risk with each country in our case studies and how this concerns future global water resources.

  10. THE POLITICS OF RISK AND EU GOVERNANCE OF HUMAN MATERIAL.

    Science.gov (United States)

    Farrel, Anne-Maree

    2009-03-01

    This paper examines the politics of EU risk governance in relation to human material. It is argued that the political context has informed the way in which risks in relation to various types of human material have come to be defined as policy problems at EU level. In turn, this has influenced the design and/or persistence of institutional arrangements to manage such problems. It is further argued that this political context has resulted in a significant level of disconnection in risk governance in the area. This has happened in two ways. First, there has been a growing level of disconnection between institutional and stakeholder demands for a more expansive approach to risk governance in the area and the narrowly-circumscribed competence under Article 152(4)(a) EC, which permits the adoption of risk regulation regimes that set minimum standards of quality and safety in relation to blood, tissue/cells and organs. Second, it has led to the development of institutional arrangements that promote a bifurcated approach to risk governance, specifically in relation to blood and tissues/cells. Although a hybrid of traditional and new governance mechanisms have been employed to address this problem of disconnection, this has nevertheless added a further layer to already complex institutional arrangements for risk governance in the area. It is suggested that a more integrated approach to EU risk governance in relation to human material is needed. Implementing such an approach would contribute to greater clarity, transparency and accountability in decision-making processes, and this could enhance public trust in what is a politically-sensitive area of governance at EU level.

  11. A Novel Approach: Chemical Relational Databases, and the Role of the ISSCAN Database on Assessing Chemical Carcinogenity

    Science.gov (United States)

    Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did no...

  12. Assessment factors for human health risk assessment: A discussion paper

    NARCIS (Netherlands)

    Vermeire, T.; Stevenson, H.; Pieters, M.N.; Rennen, M.; Slob, W.; Hakkert, B.C.

    1999-01-01

    The general goal of this discussion paper is to contribute toward the further harmonization of human health risk assessment. It first discusses the development of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factor

  13. The High-mountain Cryosphere: Environmental Changes and Human Risks

    Directory of Open Access Journals (Sweden)

    Maria Shahgedanova

    2016-08-01

    Full Text Available Reviewed: The High-mountain Cryosphere: Environmental Changes and Human Risks Edited by Christian Huggel, Mark Carey, John J. Clague, and Andreas Kääb. Cambridge, UK: Cambridge University Press, 2015. xii + 363 pp. Hardcover: US$ 140.00, ISBN 978-1-107-06584-0. E-book: US$ 112.00, ISBN 978-1-316-35515-2.

  14. Human health risks in an old gold mining area with circum-neutral drainage, central Portugal.

    Science.gov (United States)

    Carvalho, P C S; Neiva, A M R; Silva, M M V G; Santos, A C T

    2017-02-01

    The former mine of Escádia Grande was active at the middle of 1900 and was exploited for Au and Ag. The mineralized quartz veins consist mainly of quartz, arsenopyrite, pyrite, rare chalcopyrite, galena, sphalerite, gold and argentite. The mine dumps and tailings were deposited close to a stream, and there is a river beach downstream used for recreational proposes. Two villages are also located close to the old mining area. Mine wastes contained up to 8090 mg/kg of As and 70.1 mg/kg of Sb. The waters of the stream that cross the mining area have circum-neutral pH values and contained elevated concentrations of As reaching up to 284 µg/L. However, geochemical speciation modeling (Phreeq C) revealed that As was mainly present as As (V). Arsenic concentrations in waters are attenuated throughout the stream, mainly by the iron-(hydro)-oxides adsorption upstream. However, at 2 km downstream of mine wastes in the river beach, the waters still exceeded 10 µg/L of As, the drinking water limit. The waters also have NO2(-), Cu and Cd concentrations higher than drinking water limit. The stream sediments have As concentrations up to 45 times higher (3140 mg/kg) than the limit of the sediment guideline values of NWQMS (2000). The maximum arsenic concentrations in soils are also up to 27 times higher (5940 mg/kg) than the maximum concentrations in streams from FOREGS Geochemical Atlas of Europe. The use of river beach for recreational purposes causes cancer risk (4.48 × 10(-6)) higher than USEPA limit, mainly due to the arsenic exposure. Even for recreational purposes, stream sediments and soils in the old mining area have high non-carcinogenic effects (2.76 and 4.78, respectively) for children, also related to the arsenic exposure mainly by the ingestion pathway, and the risk is unacceptable according to the limits of USEPA. Moreover, the cancer risk resulting from exposure of adults to arsenic in soils also has unacceptable non-cancer risk (1.13). Arsenic is the

  15. EPA`s program for risk assessment guidelines: Cancer classification issues

    Energy Technology Data Exchange (ETDEWEB)

    Wiltse, J. [Environmental Protection Agency, Washington, DC (United States)

    1990-12-31

    Issues presented are related to classification of weight of evidence in cancer risk assessments. The focus in this paper is on lines of evidence used in constructing a conclusion about potential human carcinogenicity. The paper also discusses issues that are mistakenly addressed as classification issues but are really part of the risk assessment process. 2 figs.

  16. Human and animal sentinels for shared health risks

    Directory of Open Access Journals (Sweden)

    Peter Rabinowitz, MD, MPH

    2009-03-01

    Full Text Available The tracking of sentinel health events in humans in order to detect and manage disease risks facing a larger population is a well accepted technique applied to influenza, occupational conditions and emerging infectious diseases. Similarly, animal health professionals routinely track disease events in sentinel animal colonies and sentinel herds. The use of animals as sentinels for human health threats, or of humans as sentinels for animal disease risk, dates back at least to the era when coal miners brought caged canaries into mines to provide early warning of toxic gases. Yet the full potential of linking animal and human health information to provide warning of such ‘shared risks’ from environmental hazards has not been realised. Reasons appear to include the professional segregation of human and animal health communities, the separation of human and animal surveillance data and evidence gaps in the linkages between human and animal responses to environmental health hazards. The ‘One Health initiative’ and growing international collaboration in response to pandemic threats, coupled with development in the fields of informatics and genomics, hold promise for improved sentinel event coordination in order to detect and reduce environmental health threats shared between species.

  17. Reevaluating the carcinogenicity of ortho-toluidine: a new conclusion and its implications.

    Science.gov (United States)

    Sellers, C; Markowitz, S

    1992-12-01

    The aromatic amine ortho-toluidine has been recognized by IARC as an animal carcinogen for the past decade. Three recent epidemiological studies of worker populations have now implicated this chemical as a human bladder carcinogen. In a study by E. Ward, A. Carpenter, S. Markowitz, D. Roberts, and W. Halperin ((1991), J. Natl. Cancer Inst. 83, 501-506), workers definitely exposed to ortho-toluidine for at least 10 years experienced a Standardized Incidence Ratio (SIR) of 27.2 (90% CI = 11.8-53.7). The other major exposure was to aniline, which significant epidemiological studies have failed to confirm as a human carcinogen. In retrospect, studies by G. F. Rubino, G. Scansetti, G. Piolatto ((1982) Environ. Res. 27, 241-254) and M. J. Stasik ((1988) Int. Arch. Occup. Environ. Health 60, 21-24) also support the hypothesis that ortho-toluidine is a human bladder carcinogen. Animal studies of both ortho-toluidine and its possible confounders in these epidemiological investigations further confirm this hypothesis. When evaluated in a suitably comprehensive way, according to the traditional standards for assessing causality outlined by A. B. Hill ((1977) A Short Textbook of Medical Statistics, pp. 288-294, Lippincott, Philadelphia) the evidence that ortho-toluidine causes human bladder cancer has become much more conclusive. In this case, animal tests have proven a good predictor of human carcinogenicity.

  18. Credit scores, cardiovascular disease risk, and human capital.

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  19. Credit scores, cardiovascular disease risk, and human capital

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E.

    2014-01-01

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions. PMID:25404329

  20. Influence of tobacco smoke on carcinogenic PAH composition in indoor PM 10 and PM 2.5

    Science.gov (United States)

    Slezakova, K.; Castro, D.; Pereira, M. C.; Morais, S.; Delerue-Matos, C.; Alvim-Ferraz, M. C.

    2009-12-01

    Because of the mutagenic and/or carcinogenic properties, Polycyclic Aromatic Hydrocarbons (PAH), have a direct impact on human population. Consequently, there is a widespread interest in analysing and evaluating the exposure to PAH in different indoor environments, influenced by different emission sources. The information on indoor PAH is still limited, mainly in terms of PAH distribution in indoor particles of different sizes; thus, this study evaluated the influence of tobacco smoke on PM 10 and PM 2.5 characteristics, namely on their PAH compositions, with further aim to understand the negative impact of tobacco smoke on human health. Samples were collected at one site influenced by tobacco smoke and at one reference (non-smoking) site using low-volume samplers; the analyses of 17 PAH were performed by Microwave Assisted Extraction combined with Liquid Chromatography (MAE-LC). At the site influenced by tobacco smoke PM concentrations were higher 650% for PM 10, and 720% for PM 2.5. When influenced by smoking, 4 ring PAH (fluoranthene, pyrene, and chrysene) were the most abundant PAH, with concentrations 4600-21 000% and 5100-20 800% higher than at the reference site for PM 10 and PM 2.5, respectively, accounting for 49% of total PAH (Σ PAH). Higher molecular weight PAH (5-6 rings) reached concentrations 300-1300% and 140-1700% higher for PM 10 and PM 2.5, respectively, at the site influenced by tobacco smoke. Considering 9 carcinogenic PAH this increase was 780% and 760% in PM 10 and PM 2.5, respectively, indicating the strong potential risk for human health. As different composition profiles of PAH in indoor PM were obtained for reference and smoking sites, those 9 carcinogens represented at the reference site 84% and 86% of Σ PAH in PM 10 and PM 2.5, respectively, and at the smoking site 56% and 55% of Σ PAH in PM 10 and PM 2.5, respectively. All PAH (including the carcinogenic ones) were mainly present in fine particles, which corresponds to a strong risk

  1. An exploration of spatial human health risk assessment of soil toxic metals under different land uses using sequential indicator simulation.

    Science.gov (United States)

    Huang, Jin-Hui; Liu, Wen-Chu; Zeng, Guang-Ming; Li, Fei; Huang, Xiao-Long; Gu, Yan-Ling; Shi, Li-Xiu; Shi, Ya-Hui; Wan, Jia

    2016-07-01

    A modified method was proposed which integrates the spatial patterns of toxic metals simulated by sequential indicator simulation, different exposure models and local current land uses extracted by remote-sensing software into a dose-response model for human health risk assessment of toxic metals. A total of 156 soil samples with a various land uses containing farm land (F1-F25), forest land (W1-W12) and residential land (U1-U15) were collected in a grid pattern throughout Xiandao District (XDD), Hunan Province, China. The total Cr and Pb in topsoil were analyzed. Compared with Hunan soil background values, the elevated concentrations of Cr were mainly located in the east of XDD, and the elevated concentrations of Pb were scattered in the areas around F1, F6, F8, F13, F14, U5, U14, W2 and W11. For non-carcinogenic effects, the hazard index (HI) of Cr and Pb overall the XDD did not exceed the accepted level to adults. While to children, Cr and Pb exhibited HI higher than the accepted level around some areas. The assessment results indicated Cr and Pb should be regarded as the priority pollutants of concern in XDD. The first priority areas of concern were identified in region A with a high probability (>0.95) of risk in excess of the accepted level for Cr and Pb. The areas with probability of risk between 0.85 and 0.95 in region A were identified to be the secondary priority areas for Cr and Pb. The modified method was proved useful due to its improvement on previous studies and calculating a more realistic human health risk, thus reducing the probability of excessive environmental management.

  2. Addressing Human System Risks to Future Space Exploration

    Science.gov (United States)

    Paloski, W. H.; Francisco, D. R.; Davis, J. R.

    2015-01-01

    NASA is contemplating future human exploration missions to destinations beyond low Earth orbit, including the Moon, deep-space asteroids, and Mars. While we have learned much about protecting crew health and performance during orbital space flight over the past half-century, the challenges of these future missions far exceed those within our current experience base. To ensure success in these missions, we have developed a Human System Risk Board (HSRB) to identify, quantify, and develop mitigation plans for the extraordinary risks associated with each potential mission scenario. The HSRB comprises research, technology, and operations experts in medicine, physiology, psychology, human factors, radiation, toxicology, microbiology, pharmacology, and food sciences. Methods: Owing to the wide range of potential mission characteristics, we first identified the hazards to human health and performance common to all exploration missions: altered gravity, isolation/confinement, increased radiation, distance from Earth, and hostile/closed environment. Each hazard leads to a set of risks to crew health and/or performance. For example the radiation hazard leads to risks of acute radiation syndrome, central nervous system dysfunction, soft tissue degeneration, and carcinogenesis. Some of these risks (e.g., acute radiation syndrome) could affect crew health or performance during the mission, while others (e.g., carcinogenesis) would more likely affect the crewmember well after the mission ends. We next defined a set of design reference missions (DRM) that would span the range of exploration missions currently under consideration. In addition to standard (6-month) and long-duration (1-year) missions in low Earth orbit (LEO), these DRM include deep space sortie missions of 1 month duration, lunar orbital and landing missions of 1 year duration, deep space journey and asteroid landing missions of 1 year duration, and Mars orbital and landing missions of 3 years duration. We then

  3. Risk management with regard to the effect of human factors

    Directory of Open Access Journals (Sweden)

    I. A. Kiseleva

    2016-01-01

    Full Text Available One of the most important components in today's market is a party decision-making under risk and uncertainty. The first step in making such decisions - to adequately process the information for estimating the future value of assets and the interests of investors probabilities of each particular scenario. The next step is to choose the alternative that has the greatest utility for the investor. Each of these steps is associated with numerous difficulties, the roots of which stem from the specificity of human psychology. The article notes that an integral part of professional risk management is to identify the nature of the object of management in the sphere of economy. Since the domestic theory of risk management is being formed-tion, the problem of a clear comprehensive definition of “risk” becomes now particularly relevant-ness. The article deals with along with economic forecasts of the risks and the human factor in decision-tions solutions. Along with economic forecasts, the report focuses on psychological problems and attempts to take into account the human factor in decision-making at the forecast of risks arising in the company. The important parameters are the status and position of the person in the society, as well as its social well-being. Analysis Meto-ing risk assessment concluded that the need to develop new models and methods of risk management, taking into account the four-lovecheskogo factor. Economic psychology and its applications have developed into a special branch of economic knowledge - the so-called behavioral economics, which surely develops a wide range of economic issues - from the actual theory of individual behavior to the problems of public choice and the financial economy. The most interesting item is the fact that the concept of “risk” is considered from different points of view - as the economist-mathematician with the position, and a psychologist.

  4. Quantifying risk factors for human brucellosis in rural northern Tanzania.

    Directory of Open Access Journals (Sweden)

    Kunda John

    Full Text Available BACKGROUND: Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. METHODS: This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. RESULTS: Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from

  5. Temporal evolution of risk estimates for presumed human teratogens.

    Science.gov (United States)

    Koebert, M K; Haun, J M; Pauli, R M

    1993-01-01

    We present preliminary data assessing a previously untried method of deriving estimates of risk from case reports on presumed human teratogens. We postulated that we could take advantage of biases inherent to case reports in order to generate one or more families of temporal curves that could be used to estimate the "true" risk of teratogenic exposure. Using this method (which we refer to as the "case-cumulative method") we found that two agents (parvovirus B19 and isotretinoin) demonstrated a logarithmic decrease in the estimated risk over time, as intuitively expected, while trimethadione and the coumarin derivatives showed a more complex pattern over time. Analysis of estimated risks quoted by reviews and large studies for these four agents showed large variability from estimate to estimate and no discernible temporal pattern. With further analysis of other agents, the case-cumulative method might eventually prove to be useful in teratogen counseling.

  6. Stochastic goal programming based groundwater remediation management under human-health-risk uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jing; He, Li, E-mail: li.he@ncepu.edu.cn; Lu, Hongwei; Fan, Xing

    2014-08-30

    Highlights: • We propose an integrated optimal groundwater remediation design approach. • The approach can address stochasticity in carcinogenic risks. • Goal programming is used to make the system approaching to ideal operation and remediation effects. • The uncertainty in slope factor is evaluated under different confidence levels. • Optimal strategies are obtained to support remediation design under uncertainty. - Abstract: An optimal design approach for groundwater remediation is developed through incorporating numerical simulation, health risk assessment, uncertainty analysis and nonlinear optimization within a general framework. Stochastic analysis and goal programming are introduced into the framework to handle uncertainties in real-world groundwater remediation systems. Carcinogenic risks associated with remediation actions are further evaluated at four confidence levels. The differences between ideal and predicted constraints are minimized by goal programming. The approach is then applied to a contaminated site in western Canada for creating a set of optimal remediation strategies. Results from the case study indicate that factors including environmental standards, health risks and technical requirements mutually affected and restricted themselves. Stochastic uncertainty existed in the entire process of remediation optimization, which should to be taken into consideration in groundwater remediation design.

  7. Human System Risk Management - Tools of our Trade

    Science.gov (United States)

    Ott, C. Mark

    2009-01-01

    The risk of infectious disease to select individuals has historically been difficult to predict in either spaceflight or on Earth with health care efforts relying on broad-based prevention and post-infection treatment. Over the past 10 years, quantitative microbial risk assessment evaluations have evolved to formalize the assessment process and quantify the risk. This process of hazard identification, exposure assessment, dose-response assessment, and risk characterization has been applied by the water and food safety industries to address the public health impacts associated with the occurrence of and human exposure to pathogens in water and food for the development of preventive strategies for microbial disease. NASA is currently investigating the feasibility of using these techniques to better understand the risks to astronauts and refine their microbiological requirements. To assess these techniques, NASA began an evaluation of the potable water system on the International Space Station to determine how the microbial risk from water consumption during flight differed from terrestrial sources, such as municipal water systems. The ultimate goal of this work is to optimize microbial requirements which would minimize unnecessary cargo and use of crew time, while still protecting the health of the crew. Successful demonstration of this risk assessment framework with the water system holds the potential to maximize the use of available resources during spaceflight missions and facilitate investigations into the evaluation of other routes of infection, such as through the spaceflight foods system.

  8. Human System Risk Management - Tools of our Trade

    Science.gov (United States)

    Ott, C. Mark

    2009-01-01

    The risk of infectious disease to select individuals has historically been difficult to predict in either spaceflight or on Earth with health care efforts relying on broad-based prevention and post-infection treatment. Over the past 10 years, quantitative microbial risk assessment evaluations have evolved to formalize the assessment process and quantify the risk. This process of hazard identification, exposure assessment, dose-response assessment, and risk characterization has been applied by the water and food safety industries to address the public health impacts associated with the occurrence of and human exposure to pathogens in water and food for the development of preventive strategies for microbial disease. NASA is currently investigating the feasibility of using these techniques to better understand the risks to astronauts and refine their microbiological requirements. To assess these techniques, NASA began an evaluation of the potable water system on the International Space Station to determine how the microbial risk from water consumption during flight differed from terrestrial sources, such as municipal water systems. The ultimate goal of this work is to optimize microbial requirements which would minimize unnecessary cargo and use of crew time, while still protecting the health of the crew. Successful demonstration of this risk assessment framework with the water system holds the potential to maximize the use of available resources during spaceflight missions and facilitate investigations into the evaluation of other routes of infection, such as through the spaceflight foods system.

  9. Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid.

    Science.gov (United States)

    Alisson-Silva, Frederico; Kawanishi, Kunio; Varki, Ajit

    2016-10-01

    One of the most consistent epidemiological associations between diet and human disease risk is the impact of red meat consumption (beef, pork, and lamb, particularly in processed forms). While risk estimates vary, associations are reported with all-cause mortality, colorectal and other carcinomas, atherosclerotic cardiovascular disease, type II diabetes, and possibly other inflammatory processes. There are many proposed explanations for these associations, some long discussed in the literature. Attempts to explain the effects of red meat consumption have invoked various red meat-associated agents, including saturated fat, high salt intake, Trimethylamine-N-oxide (TMAO) generation by microbiota, and environmental pollutants contaminating red meat, none of which are specific for red meat. Even the frequently mentioned polycyclic aromatic carcinogens arising from high temperature cooking methods are not red meat specific, as these are also generated by grilling poultry or fish, as well as by other forms of cooking. The traditional explanations that appear to be more red meat specific invoke the impact of N-nitroso compounds, heme iron, and the potential of heme to catalyze endogenous nitrosation. However, heme can be denatured by cooking, high levels of plasma hemopexin will block its tissue delivery, and much higher amounts of heme likely originate from red blood cell breakdown in vivo. Therefore, red meat-derived heme could only contribute to colorectal carcinoma risk, via direct local effects. Also, none of these mechanisms explain the apparent human propensity i.e., other carnivores have not been reported at high risk for all these diseases. A more recently proposed hypothesis involves infectious agents in beef from specific dairy cattle as agents of colorectal cancer. We have also described another mechanistic explanation for the human propensity for risk of red-meat associated diseases that is consistent with most observations: metabolic incorporation of a non-human

  10. Cell-mediated mutagenesis by chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Huberman, E.; Langenbach, R.

    1978-01-01

    The cell-mediated mutation system, with the proper choice of metabolizing cells, can be used to detect the mutagenic activities of different classes of chemical carcinogens. When fibroblastic cells were used as the metabolizing cells, a correlation between the in vivo carcinogenic activity and the in vitro mutagenic activity of 11 aromatic polycyclic hydrocarbons was observed. When primary liver cells were used as the metabolizing cells, three known liver carcinogens were demonstrated to be mutagenic by the cell-mediated assay, while two non-carcinogenic analogues were not mutagenic. These results from the cell-mediated system suggest that the reactive intermediates of the carcinogens are stable enough to be transferred from the metabolizing cells to the V79 cells. The cell-mediated mutagenesis system is a simple in vitro assay which may simulate the in vivo situation. It was concluded that this approach could be extended to the co-cultivation of cells from other organs or tissues with mutable mammalian cells.

  11. Lung cancer risk in relation to dietary acrylamide intake

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Background : Acrylamide is a probable human carcinogen that is present in several heat-treated foods. In epidemiological studies, positive associations between dietary acrylamide intake and the risks of endometrial, ovarian, estrogen receptor-positive breast, and renal cell cancers have been observe

  12. Lung cancer risk in relation to dietary acrylamide intake

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Background : Acrylamide is a probable human carcinogen that is present in several heat-treated foods. In epidemiological studies, positive associations between dietary acrylamide intake and the risks of endometrial, ovarian, estrogen receptor-positive breast, and renal cell cancers have been

  13. Seafood consumption among Chinese coastal residents and health risk assessment of heavy metals in seafood.

    Science.gov (United States)

    Zhao, Ran; Yan, Shuangshuang; Liu, Min; Wang, Bi; Hu, Dong; Guo, Dongbei; Wang, Juan; Xu, Wanting; Fan, Chun

    2016-08-01

    The aims of the present study were to obtain the seafood dietary patterns of coastal residents, to determine the concentrations of heavy metals, and to evaluate the possible health risks caused by seafood intake. The daily food intakes of 24 types of seafood were collected from 738 participants from Xiamen, a southern Chinese coastal city, using food frequency questionnaire (FFQ) and dietary history method. One hundred and fifty-six samples of 14 types of highest intake seafood were collected from local markets for lead (Pb), cadmium (Cd), chromium (Cr), mercury (Hg), and arsenic (As) determination. Health risks via seafood consumption were evaluated by calculating the target hazard quotient (THQ) and the total hazard index (HI) for carcinogenic and non-carcinogenic effects recommended by the US Environmental Protection Agency. The results showed that the seafood daily intake of Xiamen residents was 61.5 (2.14, 115) g/day. The concentrations of Pb, Cd, Cr, Hg, and As in seafood were ND-0.45 mg/kg, ND-0.19 mg/kg, ND-0.80 mg/kg, ND-0.70 mg/kg, and 0.32-16.9 mg/kg, respectively. Concentrations of Cd and As in some samples were higher than national limitation standards. Consumption of 14 common types of seafood would not pose non-carcinogenic risk. However, some types, such as sparuslatus, oyster, and porphyra tenera, would form a carcinogenic risk. Regardless of a carcinogenic or non-carcinogenic risk, As posed the highest risk on humans. The observed HI value for non-carcinogenic effect of all metals in all seafood reached 0.69-2.20, and the metal orders of risk can be listed as As > Hg > Cr > Cd > Pb, reiterating the risk of As is a matter of concern in seafood from Xiamen markets.

  14. Carcinogenicity and genotoxicity of ethylene oxide: new aspects and recent advances.

    Science.gov (United States)

    Thier, R; Bolt, H M

    2000-09-01

    Long-term inhalation studies in rodents have presented unequivocal evidence of experimental carcinogenicity of ethylene oxide, based on the formation of malignant tumors at multiple sites. However, despite a considerable body of epidemiological data only limited evidence has been obtained of its carcinogenicity in humans. Ethylene oxide is not only an important exogenous toxicant, but it is also formed from ethylene as a biological precursor. Ethylene is a normal body constituent; its endogenous formation is evidenced by exhalation in rats and in humans. Consequently, ethylene oxide must also be regarded as a physiological compound. The most abundant DNA adduct of ethylene oxide is 7-(2-hydroxyethyl)guanine (HOEtG). Open questions are the nature and role of tissue-specific factors in ethylene oxide carcinogenesis and the physiological and quantitative role of DNA repair mechanisms. The detection of remarkable individual differences in the susceptibility of humans has promoted research into genetic factors that influence the metabolism of ethylene oxide. With this background it appears that current PBPK models for trans-species extrapolation of ethylene oxide toxicity need to be refined further. For a cancer risk assessment at low levels of DNA damage, exposure-related adducts must be discussed in relation to background DNA damage as well as to inter- and intraindividual variability. In rats, subacute ethylene oxide exposures on the order of 1 ppm (1.83 mg/m3) cause DNA adduct levels (HOEtG) of the same magnitude as produced by endogenous ethylene oxide. Based on very recent studies the endogenous background levels of HOEtG in DNA of humans are comparable to those that are produced in rodents by repetitive exogenous ethylene oxide exposures of about 10 ppm (18.3 mg/m3). Experimentally, ethylene oxide has revealed only weak mutagenic effects in vivo, which are confined to higher doses. It has been concluded that long-term human occupational exposure to low airborne

  15. Trace Elements Contamination and Human Health Risk Assessment in Drinking Water from the Agricultural and Pastoral Areas of Bay County, Xinjiang, China.

    Science.gov (United States)

    Turdi, Muyessar; Yang, Linsheng

    2016-09-23

    Tap water samples were collected from 180 families in four agricultural (KYR: Keyir, KRW: Kariwak, YTR: Yatur, DW: Dawanqi) and two pastoral areas (B: Bulong and Y: Yangchang) in Bay County, Xinjiang, China, and levels of seven trace elements (Cd, Cr, As Ni, Pb, Zn, Se) were analyzed using inductively-coupled plasma mass spectrometry (ICP-MS) to assess potential health risks. Remarkable spatial variations of contamination were observed. Overall, the health risk was more severe for carcinogenic versus non-carcinogenic pollutants due to heavy metal. The risk index was greater for children overall (Cr > As > Cd and Zn > Se for carcinogenic and non-carcinogenic elements, respectively). The total risk index was greater in agricultural areas (DW > KYR > YTR > KRW > B > Y). Total risk indices were greater where well water was the source versus fountain water; for the latter, the total health risk index was greater versus glacier water. Main health risk factors were Cr and As in DW, KYR, YTR, KRW, and B, and Zn, Cr, and As in the Y region. Overall, total trace element-induced health risk (including for DW adults) was higher than acceptable (10(-6)) and lower than priority risk levels (10(-4)) (KYR, YTR, KRW, Y, and B). For DW children, total health risk reached 1.08 × 10(-4), higher than acceptable and priority risk levels (10(-4)).

  16. Human Health and Ecological Risk Assessment for the Operation of the Explosives Waste Treatment Facility at Site 300 of the Lawrence Livermore National Laboratory, Volume 1: Report of Results

    Energy Technology Data Exchange (ETDEWEB)

    Gallegos, G M; Daniels, J I; Wegrecki, A M

    2005-11-07

    Human health and ecological risk assessments are required as part of the Resource Recovery and Conservation Act (RCRA) permit renewal process for waste treatment units. This risk assessment is prepared in support of the RCRA permit renewal for the Explosives Waste Treatment Facility at Site 300 of the Lawrence Livermore National Laboratory. The human health risk assessment is based on U.S. Environmental Protection Agency approved emissions factors and on California Environmental Protection Agency, Air Resources Board and U.S. Environmental Protection Agency risk assessment and air dispersion models. The risk assessment identifies receptors of concern and evaluates carcinogenic risk, and acute and chronic noncarcinogenic hazard. The carcinogenic risk to a 30-year resident at the maximum offsite receptor location is 0.0000006 or 0.6 in one million. The carcinogenic risk to a 25-year worker at the maximum bystander on-site receptor location is also 0.0000006 or 0.6 in one million. Any risk of less than 1 in a million is below the level of regulatory concern. The acute noncarcinogenic hazard for the 30-year resident is 0.02 and the chronic noncarcinogenic hazard is 0.01. The acute noncarcinogenic hazard for the 25-year worker is 0.3 and the chronic noncarcinogenic hazard is 0.2. The point of comparison for acute and chronic noncarcinogenic hazard is 1.0, an estimate less than 1.0 is below the level of regulatory concern. The estimates of health effects are based on health conservative assumptions and represent an upper bound of the possible exposures to the receptors. For the ecological risk assessment, four receptor species were evaluated for potential detrimental effects; none were found to be adversely affected because for each species the predicted ecological hazard quotients are always less than one. Based on these results, emissions from the operations of the Explosive Waste Treatment Facility should not be considered to be of concern for human health or

  17. Human health risk assessment of lead, manganese and copper from scrapped car paint dust from automobile workshops in Nigeria.

    Science.gov (United States)

    Nduka, John Kanayochukwu; Onyenezi Amuka, John Paul; Onwuka, Jude Chinedu; Udowelle, Nnaemeka Arinze; Orisakwe, Orish Ebere

    2016-10-01

    The economic downturn in Nigeria and Structural Adjustment Programme led to the flooding of Nigerian market with imported used automobiles. Most of these vehicles needed refurbishing and reworking. The present study is a human health risk assessment of metal exposure resulting from reworking of imported used vehicles in Nigeria. Scrap paint dusts from 56 Japanese made cars were collected from 8 different mechanic villages (workshops A-H] in Southeastern Nigeria. Scrap paints were homogenized, mixed, divided into fine particles and digested by standard method. The filtrates were assayed of lead, manganese and copper with atomic absorption spectrophotometry (AAS). Workshop B has the highest concentration of Pb (4.26 ± 0.93). Manganese in workshops A and F were (3.31 ± 0.85) and (3.04 ± 0.47) respectively and were higher than the levels from workshops C, B, D, G and H. Copper in workshop D (7.11 ± 0.21) was significantly greater than the other workshops. The highest hazard quotient (HQ) through ingestion, inhalation and dermal exposures in adults were 9.44E-05 (workshop B), 4.20E-01 (workshop B) and 1.08E-05 (workshop D) respectively. The highest values for HQ through ingestion, inhalation and dermal in children were 8.82E-04, 7.61E-01 and 2.86E-05 all in workshop B respectively. For children, the highest carcinogenic risk levels were 7.05E-08, 6.09E-05 and 2.29E-10 for ingestion, inhalation and dermal exposures respectively. In adults, the carcinogenic risk levels were 7.55E-09, 3.39E-05 and 8.67E-10 for ingestion, inhalation and dermal exposures respectively. Chronic exposure to scrap car paint dusts may be of significant public health importance in Nigeria as this may add to the body burden of some heavy metals.

  18. Spatial Distribution and Fuzzy Health Risk Assessment of Trace Elements in Surface Water from Honghu Lake.

    Science.gov (United States)

    Li, Fei; Qiu, Zhenzhen; Zhang, Jingdong; Liu, Chaoyang; Cai, Ying; Xiao, Minsi

    2017-09-04

    Previous studies revealed that Honghu Lake was polluted by trace elements due to anthropogenic activities. This study investigated the spatial distribution of trace elements in Honghu Lake, and identified the major pollutants and control areas based on the fuzzy health risk assessment at screening level. The mean total content of trace elements in surface water decreased in the order of Zn (18.04 μg/L) > Pb (3.42 μg/L) > Cu (3.09 μg/L) > Cr (1.63 μg/L) > As (0.99 μg/L) > Cd (0.14 μg/L), within limits of Drinking Water Guidelines. The results of fuzzy health risk assessment indicated that there was no obvious non-carcinogenic risk to human health, while carcinogenic risk was observed in descending order of As > Cr > Cd > Pb. As was regarded to have the highest carcinogenic risk among selected trace elements because it generally accounted for 64% of integrated carcinogenic risk. Potential carcinogenic risk of trace elements in each sampling site was approximately at medium risk level (10(-5) to 10(-4)). The areas in the south (S4, S13, and S16) and northeast (S8, S18, and S19) of Honghu Lake were regarded as the risk priority control areas. However, the corresponding maximum memberships of integrated carcinogenic risk in S1, S3, S10-S13, S15, and S18 were of relatively low credibility (50-60%), and may mislead the decision-makers in identifying the risk priority areas. Results of fuzzy assessment presented the subordinate grade and corresponding reliability of risk, and provided more full-scale results for decision-makers, which made up for the deficiency of certainty assessment to a certain extent.

  19. Mutagenicity, carcinogenicity and teratogenicity of beryllium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R

    1987-07-01

    The carcinogenicity of a number of beryllium compounds has been confirmed in experiments on laboratory animals and this metal has to be treated as a possible carcinogenic threat to man. These carcinogenic properties are associated with mutagenic activity as shown by the results of short-term tests performed in vitro with beryllium chloride and beryllium sulfate. These soluble beryllium compounds can produce some infidelity of in vitro synthesis, forward gene mutations in microorganisms and in mammalian cells. They are also able to induce cell transformation. In addition to the positive results obtained in several short-term assays beryllium compounds have been found to bind to nucleoproteins, to inhibit certain enzymes needed for DNA synthesis, to bind nucleic acids to cell membranes and to inhibit microtubule polymerization. The teratogenicity of beryllium salts is relatively unknown and needs additional investigation.

  20. Evaluation of potential human health effects associated with the agricultural uses of 1,3-D: Spatial and temporal stochastic risk analysis.

    Science.gov (United States)

    Driver, Jeffrey H; Price, Paul S; Van Wesenbeeck, Ian; Ross, John H; Gehen, Sean; Holden, Larry R; Landenberger, Bryce; Hastings, Kerry; Yan, Zhongyu June; Rasoulpour, Reza

    2016-11-15

    Dow AgroSciences (DAS) markets and sells 1,3-Dichloropropene (1,3-D), the active ingredient in Telone®, which is used as a pre-plant soil fumigant nematicide in economically important crops in California. 1,3-D has been regulated as a "probable human carcinogen" and the California Department of Pesticide Regulation limits use of 1,3-D based on human health risk assessments for bystanders. This paper presents a risk characterization for bystanders based on advances in the assessment of both exposure and hazard. The revised bystander risk assessment incorporates significant advances: 1) new data on residency duration and mobility in communities where 1,3-D is in high demand; 2) new information on spatial and temporal concentrations of 1,3-D in air based on multi-year modeling using a validated model; and 3) a new stochastic spatial and temporal model of long-term exposures. Predicted distributions of long-term, chronic exposures indicate that current, and anticipated uses of 1,3-D would result in lifetime average daily doses lower than 0.002mg/kg/d, a dose associated with theoretical lifetime excess cancer risk of 95% of the local population based on a non-threshold risk assessment approach. Additionally, examination of 1,3-D toxicity studies including new chronic toxicity data and mechanism of action supports the use of a non-linear, threshold based risk assessment approach. The estimated maximum annual average daily dose of 1000-fold, a clear indication of acceptable risk for human health. In summary, the best available science supports 1,3-D's threshold nature of hazard and the revised exposure assessment supports that current agricultural uses of 1,3-D are associated with reasonable certainty of no harm, i.e., estimated long-term exposures pose insignificant health risks to bystanders even when the non-threshold approach is assumed.

  1. Challenges to communicate risks of human-caused earthquakes

    Science.gov (United States)

    Klose, C. D.

    2014-12-01

    The awareness of natural hazards has been up-trending in recent years. In particular, this is true for earthquakes, which increase in frequency and magnitude in regions that normally do not experience seismic activity. In fact, one of the major concerns for many communities and businesses is that humans today seem to cause earthquakes due to large-scale shale gas production, dewatering and flooding of mines and deep geothermal power production. Accordingly, without opposing any of these technologies it should be a priority of earth scientists who are researching natural hazards to communicate earthquake risks. This presentation discusses the challenges that earth scientists are facing to properly communicate earthquake risks, in light of the fact that human-caused earthquakes are an environmental change affecting only some communities and businesses. Communication channels may range from research papers, books and class room lectures to outreach events and programs, popular media events or even social media networks.

  2. Quantifying Risk Factors for Human Brucellosis in Rural Northern Tanzania

    OpenAIRE

    Kunda John; Julie Fitzpatrick; Nigel French; Rudovick Kazwala; Dominic Kambarage; Mfinanga, Godfrey S; Alastair MacMillan; Sarah Cleaveland

    2010-01-01

    BACKGROUND: Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission...

  3. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  4. An industry perspective on the utility of short-term carcinogenicity testing in transgenic mice in pharmaceutical development.

    Science.gov (United States)

    Storer, Richard D; Sistare, Frank D; Reddy, M Vijayaraj; DeGeorge, Joseph J

    2010-01-01

    International guidelines allow for use of a short-term cancer bioassay (twenty-six weeks) in transgenic mice as a substitute for one of the two required long-term rodent bioassays in the preclinical safety evaluation of pharmaceuticals. The two models that have gained the widest acceptance by sponsors and regulatory authorities are the CB6F1-RasH2 mouse hemizygous for a human H-ras transgene and the B6.129N5-Trp53 mouse heterozygous for a p53 null allele. The p53(+/-) model is of particular value for compounds with residual concern that genotoxic activity may contribute to tumorigenesis. The rasH2 model is an appropriate alternative without regard to evidence of genotoxic potential. Since results from a short-term bioassay can be obtained relatively early in drug development, there is the potential for more timely assessment of cancer risk for individuals in long-term clinical trials. Use of these models in preclinical safety evaluation also significantly reduces animal use, time, and manpower. Preliminary findings indicate that prediction of two-year rat bioassay outcomes based on data from chronic rat toxicity studies, together with early assessment of carcinogenic potential in short-term transgenic models, may have the potential to increase the timeliness and efficiency of strategies for the identification of human carcinogenic hazards.

  5. [Mapping of carcinogens in the chemical production industry in the province of Ferrara].

    Science.gov (United States)

    Maldotti, M; Spagnolo, M R; Minisci, S; De Rosa, E

    2008-01-01

    This study consists in the reconnaissance of the carcinogenic risk in some processing in Ferrara. The main object is to know, to estimate and to verify the diffusion of the carcinogenic substances and to estimate the number of the exposed or potentially exposed workers. The study has interested the synthesis chemistry and polymer production, woodworking, welding on stainless steel and chromium conversion coating and chrome electroplating. The research has involved 54 factories and 436 workers estimated exposed or potentially exposed to carcinogenic substances. The survey has consisted of inspections in the working places, collection of exposure data, control of the precautionary measures and exposure determination in the case of stainless steel welding. The smallest factories had less knowledge of the risk and for this reason it is necessary to keep constant attention.

  6. Risk factors for breast cancer, including occupational exposures.

    Science.gov (United States)

    Weiderpass, Elisabete; Meo, Margrethe; Vainio, Harri

    2011-03-01

    The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

  7. High risk human papillomavirus and Epstein Barr virus in human breast milk

    Directory of Open Access Journals (Sweden)

    Glenn Wendy K

    2012-09-01

    Full Text Available Abstract Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid and in situ polymerase chain reaction (PCR techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15% from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%. Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.

  8. 小鼠模型在药物致癌性评价中的应用及研发人源化模型的意义%Application of mouse models for drug carcinogenicity testing and the need for development of humanized models

    Institute of Scientific and Technical Information of China (English)

    魏勤; 高翔; 徐平

    2013-01-01

    Carcinogenicity tests in preclinical drug safety studies have important impact on clinical trials and marketing authorization for medicines. In some developed countries, short/medium term models have been used as an additional component of the potential carcinogenicity assessment, replacing the 2-year mouse bioassay. Based on the data and information obtained from chemical carcinogenicity evaluation, in this article we overview the characteristics and recent application of these models. Then faced with the shortages of these models, the demand for developing new pharmaceuticals at home and the international circulation of pharmaceuticals, we suppose that the development of new humanized models with defects in functions of DNA damage repair; Cell cycle check-point appears to be very promising alternative models.%药物临床前安全性评价中的致癌实验对药物是否能进入临床实验和上市起着至关重要的作用.一些发达国家已经采用小鼠模型的短中期致癌实验作为附加实验,代替了传统的两年期实验.本文主要参考这些模型在致癌实验和药品致癌性评价中的已有数据及资料,对其特点和近年来的应用情况进行了概述.结合现有模型的缺陷,我国新药研发的需求和药物流通日益国际化的现状,得出研发DNA修复系统和细胞周期控制系统缺陷的人源化的转基因模型,是非常有前景的新替代模型.

  9. Carcinogenicity of individual and a mixture of dioxin-like compounds in female Harlan Sprague Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Walker, N.; Nyska, A. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Crockett, P. [Constella Group, Research Triangle Park, NC (US)] (and others)

    2004-09-15

    The human health risk posed by exposure to persistent organochlorine pollutants (POPs), including polychlorinated-dioxins (PCDDs), -furans (PCDFs) and - biphenyls (PCBs), present in the food and the environment is one of widespread concern throughout the industrialized world. The dioxin Toxic Equivalency Factor (TEF) approach is currently the most feasible interim approach for assessing and managing the risk posed by exposure to mixtures of these compounds and has been formally adopted by regulatory bodies in many countries, the International Programme on Chemical Safety and the World Health Organization. The TEF methodology is a relative potency scheme that estimates the total exposure and biological effects of a mixture of chemicals based on a common mechanism of action involving an initial binding of the compound to the Aryl hydrocarbon receptor (AhR). An implicit assumption of the TEF methodology is that the combined risk of effects of the different congeners is dose additive. Therefore, the total dioxin toxic equivalents (TEQs) of a mixture of PCDDs, PCDFs, and PCBs may be estimated by the summation of the mass of each compound in the mixture after adjustment for its potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While dose additivity is supported for certain mixtures for some biological endpoints in some experimental models, this has never been evaluated for cancer risk. Here we present a summary of four chronic rodent bioassay conducted by the National Toxicology Program (US Department of Health and Human Services) that evaluated the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3.3',4,4',5- pentachlorobiphenyl (PCB126) and 2,3,4,7,8 pentachlorodibenzofuran (PeCDF) and a mixture of these three dioxin-like compounds in female Harlan Sprague Dawley rats. Data from these studies will be used to test the hypothesis of dose-additivity of carcinogenicity by a defined mixture of dioxin-like compounds.

  10. Heavy metals in vegetables and potential risk for human health

    Directory of Open Access Journals (Sweden)

    Fernando Guerra

    2012-02-01

    Full Text Available Ingestion of vegetables containing heavy metals is one of the main ways in which these elements enter the human body. Once entered, heavy metals are deposited in bone and fat tissues, overlapping noble minerals. Slowly released into the body, heavy metals can cause an array of diseases. This study aimed to investigate the concentrations of cadmium, nickel, lead, cobalt and chromium in the most frequently consumed foodstuff in the São Paulo State, Brazil and to compare the heavy metal contents with the permissible limits established by the Brazilian legislation. A value of intake of heavy metals in human diets was also calculated to estimate the risk to human health. Vegetable samples were collected at the São Paulo General Warehousing and Centers Company, and the heavy metal content was determined by atomic absorption spectrophotometry. All sampled vegetables presented average concentrations of Cd and Ni lower than the permissible limits established by the Brazilian legislation. Pb and Cr exceeded the limits in 44 % of the analyzed samples. The Brazilian legislation does not establish a permissible limit for Co contents. Regarding the consumption habit of the population in the São Paulo State, the daily ingestion of heavy metals was below the oral dose of reference, therefore, consumption of these vegetables can be considered safe and without risk to human health.

  11. Tobacco-specific Carcinogen 4-(Methylnitrosoamino)-1-(3-pyridyl )-1-butanone(NNK) Activating ERK1/2 MAP Kinases and Stimulating Proliferation of Hmnan Mammary Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Cigarette smoking is correlated with the development of various cancers. 4 - (Methylnitrosoamino) -1 - ( 3 -pyridyl) -1-butanone (NNK) is one of the major tobacco-specific carcinogens in the cigarette smoke, which increases the risk of breast cancer. In the present study, it was demonstrated that NNK rapidly activated ERK1 and ERK2 MAP kinases in human normal mammary epithelial cells. It was found that there are two different routes for the activation of ERK1/2with NNK. One is from nicotinic receptor nAchR to MEK1/2, and the other is from tyrosine kinase containing receptor to MEK1/2. The tobacco-specific carcinogen NNK shows a strong proliferative effect on normal human mammary epithelial cells and cancer mammary epithelial cells.

  12. Assessment of Heavy Metal Pollution and Health Risks in the Soil-Plant-Human System in the Yangtze River Delta, China.

    Science.gov (United States)

    Hu, Bifeng; Jia, Xiaolin; Hu, Jie; Xu, Dongyun; Xia, Fang; Li, Yan

    2017-09-10

    (0.018) > Hg (0.011) > Cr (0.010) > Pb (0.001). Therefore, Cd was most easily absorbed by crops, and different crops had different capacities to absorb HMs. The hazard quotient (HQ) represents the potential non-carcinogenic risk for an individual HM and it is an estimation of daily exposure to the human population that is not likely to represent an appreciable risk of deleterious effects during a lifetime. All the HQs of the HMs for the different age groups were significantly less than the alert value of 1.0 and were at a safe level. This indicated that citizens in the study area face low potential non-carcinogenic risk caused by HMs. The total carcinogens risks (TCRs) for children, adults, and seniors were 5.24 × 10(-5), 2.65 × 10(-5), and 2.08 × 10(-5), respectively, all of which were less than the guideline value but at the alert level. Ingestion was the main pathway of carcinogen risk to human health.

  13. Quantifying human health risks from virginiamycin used in chickens.

    Science.gov (United States)

    Cox, Louis A; Popken, Douglas A

    2004-02-01

    The streptogramin antimicrobial combination Quinupristin-Dalfopristin (QD) has been used in the United States since late 1999 to treat patients with vancomycin-resistant Enterococcus faecium (VREF) infections. Another streptogramin, virginiamycin (VM), is used as a growth promoter and therapeutic agent in farm animals in the United States and other countries. Many chickens test positive for QD-resistant E. faecium, raising concern that VM use in chickens might compromise QD effectiveness against VREF infections by promoting development of QD-resistant strains that can be transferred to human patients. Despite the potential importance of this threat to human health, quantifying the risk via traditional farm-to-fork modeling has proved extremely difficult. Enough key data (mainly on microbial loads at each stage) are lacking so that such modeling amounts to little more than choosing a set of assumptions to determine the answer. Yet, regulators cannot keep waiting for more data. Patients prescribed QD are typically severely ill, immunocompromised people for whom other treatment options have not readily been available. Thus, there is a pressing need for sound risk assessment methods to inform risk management decisions for VM/QD using currently available data. This article takes a new approach to the QD-VM risk modeling challenge. Recognizing that the usual farm-to-fork ("forward chaining") approach commonly used in antimicrobial risk assessment for food animals is unlikely to produce reliable results soon enough to be useful, we instead draw on ideas from traditional fault tree analysis ("backward chaining") to reverse the farm-to-fork process and start with readily available human data on VREF case loads and QD resistance rates. Combining these data with recent genogroup frequency data for humans, chickens, and other sources (Willems et al., 2000, 2001) allows us to quantify potential human health risks from VM in chickens in both the United States and Australia, two

  14. Probabilistic integrated risk assessment of human exposure risk to environmental bisphenol A pollution sources.

    Science.gov (United States)

    Fu, Keng-Yen; Cheng, Yi-Hsien; Chio, Chia-Pin; Liao, Chung-Min

    2016-10-01

    Environmental bisphenol A (BPA) exposure has been linked to a variety of adverse health effects such as developmental and reproductive issues. However, establishing a clear association between BPA and the likelihood of human health is complex yet fundamentally uncertain. The purpose of this study was to assess the potential exposure risks from environmental BPA among Chinese population based on five human health outcomes, namely immune response, uterotrophic assay, cardiovascular disease (CVD), diabetes, and behavior change. We addressed these health concerns by using a stochastic integrated risk assessment approach. The BPA dose-dependent likelihood of effects was reconstructed by a series of Hill models based on animal models or epidemiological data. We developed a physiologically based pharmacokinetic (PBPK) model that allows estimation of urinary BPA concentration from external exposures. Here we showed that the daily average exposure concentrations of BPA and urinary BPA estimates were consistent with the published data. We found that BPA exposures were less likely to pose significant risks for infants (0-1 year) and adults (male and female >20 years) with human long-term BPA susceptibility in relation to multiple exposure pathways, and for informing the public of the negligible magnitude of environmental BPA pollution impacts on human health.

  15. Molecular epidemiology studies on occupational and environmental exposure to mutagens and carcinogens, 1997-1999.

    Science.gov (United States)

    Srám, R J; Binková, B

    2000-03-01

    Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure--metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect--chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility--genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens.

  16. Utilization of animal studies to determine the effects and human risks of environmental toxicants (drugs, chemicals, and physical agents).

    Science.gov (United States)

    Brent, Robert L

    2004-04-01

    deficiency is compounded by the fact that there are very few toxicology studies performed in children. That is why pregnant women and children are referred to as "therapeutic orphans." When animal studies are performed with newborn and developing animals, the results demonstrate that generalizations are less applicable and less predictable than the toxicology studies in pregnant animals. Although many studies reveal that the infant and the developing animal have difficulty in metabolizing drugs and are more vulnerable to the toxic effects of environmental chemicals, there are exceptions that indicate that infant and developing animals may be less vulnerable and more resilient to some drugs and chemicals. In other words, the generalization indicating that developing animals are always more sensitive to environmental toxicants is not valid. For animal toxicology studies to be useful, animal studies have to use modern concepts of pharmacokinetics and toxicokinetics, as well as method-of-action studies to determine whether animal data can be used for determining human risk. One example is the inability to determine carcinogenic risks in humans for some drugs and chemicals that produce tumors in rodents, because the oncogenesis is the result of peroxisome proliferation, a reaction that is of diminished importance in humans. Scientists can use animal studies to study the toxicokinetic and toxicodynamic aspects of environmental toxicants, but they have to be performed with the most modern techniques and interpreted with the highest level of scholarship and objectivity. Threshold exposures, maximum permissible exposures, and toxic effects can be estimated but have to be interpreted with caution when applying them to the human. Well-performed epidemiology studies are still the best method for determining the human risk and the effects of environmental toxicants.

  17. Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

    Science.gov (United States)

    Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

    2010-01-01

    In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

  18. 40 CFR 799.9420 - TSCA carcinogenicity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA carcinogenicity. 799.9420 Section 799.9420 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... their selection. (ii) Age/weight. (A) Testing shall be started with young healthy animals as soon...

  19. Carcinogenicity, allergenicity, and lupus-inducibility of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2016-01-01

    Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from cooking fume hoods as well as are generated by diverse industries. Arylamines can be generated by cleavage of azo dyes by intestinal and skin microbiota. Some arylamines are used as drugs while others are constituents of human metabolism. Many of the arylamines are mutagenic and carcinogenic. They are generally recognized as the major cause of human bladder cancer, but arylamines can induce cancers of other organs in humans and animals. Some arylamines are allergenic, causing lupus like syndrome, or other maladies. In view of their unbiquitious nature and