Banding carcinogenic risks in developed countries: A procedural basis for qualitative assessment

Readily achieved comparative assessment of carcinogenic risks consequent upon environmental exposures may increase understanding and contribute to cancer prevention. Procedures for hazard identification and quantitative risk assessment are established, but limited when addressing novel exposures to previously known carcinogens or any exposure to agents having only suspected carcinogenic activity. To complement other means of data evaluation, a procedure for qualitative assessment of carcinogenic risk is described. This involves categorizing the relevant carcinogen and circumstances under which exposure occurs. The categories for carcinogens are those used for hazard identification and involve whether the agent is (1) a recognized carcinogen for humans; (2) probably or (3) possibly carcinogenic for humans; (4) characterized by inadequate evidence of carcinogenicity; or (5) lacking carcinogenicity. Exposure is categorized by whether it is one which (1) establishes the agent as a recognized carcinogen; (2) is taken into account in establishing carcinogenicity status; (3) is distinct from those providing clearest evidence of carcinogenicity; (4) is not characterized in relation to carcinogenicity; or (5) involves an exposure in which absence of carcinogenic outcome is observed. These two categories of evidence allow the risk inherent in a situation to be banded as indicative of a proven, likely, inferred, unknown or unlikely carcinogenic outcome, and further characterized using sub-bands. The procedure has been applied to about fifty situations. For recognized carcinogens, including asbestos and polycyclic aromatic hydrocarbons, risks consequent upon occupational exposure, the impact of point source pollution, residence near contaminated sites and general environmental exposure are allocated across the proven band and a likely sub-band. For solvents, pesticides and other compounds having less clearly established carcinogenicity, impact on residents living near a production site, or near earlier related industrial activity is allocated to certain inferred sub-bands. Unknown carcinogenic outcome, which identifies exposure to an agent with inadequate evidence of carcinogenicity rather than being indicative of equivocal or negative data in any context, indicates both the impact of certain pollutants and user-exposure to some consumer products. Situations allocated to the unlikely risk band principally involve certain consumer products. Overall, such risk assessment may be of greatest worth in focusing community attention on proven causes of cancer and associated preventive measures.     

Hazardous metals levels in groundwater from Gokana,Rivers State,Nigeria: Non-cancer and cancer health risk assessment

This study investigated heavy metals concentration in groundwater in six coastal communities in Gokana, Rivers State, namely, Gbe, K-Dere, B-Dere, Mogho, Kpor and Bodo City and the human health risk posed to the local populace via ingestion and dermal contact using non-carcinogenic and carcinogenic health risk assessment. The mean values of the heavy metals ranged between 0.02–0.86, 0.16–0.19, 0.03–0.10, 0.02–0.03 and 0.01–0.17 for Mn, Ni, Pb, Cd and Cr, respectively. The heavy metals were above the drinking water quality recommended limits in all the study sites. Estimations of average daily dose (ADD) and dermal absorbed dose (DAD) health risk indicates that Mn, Ni and Pb posed human health risk via ingestion contact pathway. However, hazard index (HI) values of Cd and Cr for ingestion pathway were >1.0 and the estimated Lifetime of Carcinogenic Risks (LTCR) for Ni, Cd and Cr exceeded the predicted lifetime risk for carcinogens of 10^?6 from ingestion pathway. Furthermore, there were more appreciable risk from Ni and Cr in the study sites as LTCR value in most sites were >10^?4_. This study indicates possible non-carcinogenic and carcinogenic human health hazard from groundwater consumption in Gokana via oral ingestion.     

Roles of UDP-Glucuronosyltransferases in Chemical Carcinogenesi

Abstract

UDP-glucuronosyltransferases (UGT) play a major role in the elimination of nucleophilic metabolites of carcinogens, such as phenols and quinols of polycyclic aromatic hydrocarbons. In this way they prevent their further oxidation to electrophiles, which may react with DNA, RNA, and protein. They also inactivate carcinogenic, N-oxidized metabolites of aromatic amines. Furthermore, glucuronides may be stable transport forms of proximate carcinogens excreted via the CCor urinary tract, thereby liberating the ultimate carcinogen at the target of carcinogenicity. Isozymes of the UGT enzyme super family that control the glucuronidation of metabolites of aromatic hyharbons and of N-oxidized aromatic amines have been identified in rats and humans. Phenol UGT appears to be conduced with other drug-metabolizing enzymes via the Ah or dioxin receptor. This isozyme probably controls various proximate carcinogens and contributes to the persistently altered enzyme pattern, leading to the “toxin-resistance phenotype” at cancer prestages. Knowledge about UGTs in different species, their regulation, and their tissue distribution will improve the risk assessment of carcinogens.     

Roles of UDP-glucuronosyltransferases in chemical carcinogenesis

UDP-glucuronosyltransferases (UGT) play a major role in the elimination of nucleophilic metabolites of carcinogens, such as phenols and quinols of polycyclic aromatic hydrocarbons. In this way they prevent their further oxidation to electrophiles, which may react with DNA, RNA, and protein. They also inactivate carcinogenic, N-oxidized metabolites of aromatic amines. Furthermore, glucuronides may be stable transport forms of proximate carcinogens excreted via the biliary or urinary tract, thereby liberating the ultimate carcinogen at the target of carcinogenicity. Isozymes of the UGT enzyme superfamily that control the glucuronidation of metabolites of aromatic hydrocarbons and of N-oxidized aromatic amines have been identified in rats and humans. Phenol UGT appears to be coinduced with other drug-metabolizing enzymes via the Ah or dioxin receptor. This isozyme probably controls various proximate carcinogens and contributes to the persistently altered enzyme pattern, leading to the "toxin-resistance phenotype" at cancer prestages. Knowledge about UGTs in different species, their regulation, and their tissue distribution will improve the risk assessment of carcinogens.     

Evaluation and Spatial Diffusion of Health Risk of Persistent Organic Pollutants (POPs) in Soils Surrounding Chemical Industrial Parks in China

A case study of the cancer risk to humans posed by persistent organic pollutants (POPs) in an industrial area of China, which has a long history of contamination from many sources, is presented. Relatively great concentrations of POPs around the chemical industrial parks have the potential to be chronically carcinogenic to local people. Sixteen individual PAHs listed for priory control by the U.S. Environmental Protection Agency (USEPA), metabolites of DDTs, and isomers of HCHs were measured in soils and a human health risk assessment was conducted by use of USEPA exposure models for children and adults, respectively. Geostatistical methods were used to simulate the spatial diffusion of potential carcinogenic risk, and non-parametric Mann-Whitney U and Kruskal-Wallis tests were employed to analyze the impact of point sources on the surrounding area. The mean value of the sum of Excess Lifetime Cancer Risk (∑ELCR) exceeded the generally acceptable risk level of 1.0E-06 recommended by the USEPA for carcinogenic chemicals. The maximum ∑ELCR was 2.9E-04 for children, which was observed inside the chemical industrial parks. Contamination at the chemical industrial parks caused significant spatial diffusion of ELCR values caused by PAHs, DDT, and HCH.     

Emission sources and probabilistic health risk of volatile organic compounds emitted from production areas in a petrochemical refinery in Hainan,China

Abstract

The emission sources and health risks of volatile organic compounds (VOCs) were analyzed and evaluated in a typical petrochemical refinery in Hainan, China. The sources and levels of 9 VOCs in five production areas were identified and qualified, and the probabilistic risk assessment method was employed to obtain more reasonable and scientific outcomes specifically realized by inhalation risk model and Monte Carlo simulation. Sensitivity and uncertainty analysis were also conducted to determine the influential factors in the risk evaluation process. The results indicated that for the refinery benzene, toluene, ethyl benzene, and xylene were the primary pollutants in these production areas, where the aromatic hydrocarbon extraction device (AHED) and xylene fractionation device areas are main contributors. In terms of non-carcinogenic risk, the largest hazard index existed in AHED area. The non-carcinogenic risk values for all production areas were not more than 1. The risk value of substances such as benzene still exceed the carcinogenic risk value of 10^?6, indicating these substances existed potential carcinogenic risk to workers. Meanwhile, the findings can help to accumulate basic data for VOCs research in different installations of refineries, and provide evidence for VOCs pollution prevention and control.     

Rodent tumor profiles, Salmonella mutagenicity and risk assessment

The tumorigenesis profiles of 116 chemicals, which proved to induce cancer in the NCI/NTP experimentation, were studied by multivariate data analysis methods. Three main patterns of tumor induction were evident. One chemical (benzene) was not classifiable in any of the 3 clusters of chemicals. The carcinogen classes based on patterns of tumor induction did not reflect a repartition between Ames-positive and Ames-negative chemicals. Therefore any classification of carcinogens as either 'primary' (genotoxic, hence assumed to pose a greater risk) or 'secondary' (presumably carcinogenic via non-genotoxic mechanisms) would seem to be a subject for research and speculation, and, for the present, an unsuitable basis for risk assessment.     

Mammalian cell transformation and cell-mediated mutagenesis by carcinogenic polycyclic hydrocarbons.

The introduction of a polycyclic hydrocarbon such as benzo(alpha)pyrene (BP) into normal golden hamster embryo cell cultures results, in addition to cytotoxicity, in malignant cell transformation. Studies on the effect of different doses of BP on the normal cells showed that the frequency of transformed colonies was directly related to the dose of the carcinogen. Analysis of this dose-response curve suggests a one-event ("one-hit") response for transformation by this carcinogen. The one-event response for transformation by carcinogenic polycyclic hydrocarbons and the fact that these carcinogens bind to DNA in susceptible cells suggests that transformation can involve a single alteration in the genetic constitution of the treated cells. Carcinogens may, therefore, produce somatic mutations, some of which may involve the genes that control malignancy. Recently, considerable progress has been made in developing models for the study of chemical mutagenesis in mammalian cells. Using resistance to 8-azaguanine as a marker, positive correlations between mutagenicity and transformation were obtained with chemically reactive carcinogens such as N-acetoxy-N-2-fluorenyl-acetamide, N-methyl-N'-nitro-N-nitrosoguanidine and K-region epoxides of polycyclic hydrocarbons. However, no such correlations were obtained with the carcinogenic polycyclic hydrocarbons themselves, since the cell lines used in chemical mutagenesis do not metabolize these carcinogens. In order to obtain better correlations, we have developed a cell-mediated mutagenic assay with carcinogenic hydrocarbons in which Chinese hamster cells, which are susceptible for mutagenesis, were co-cultivated with lethally irradiated rodent cells that can metabolize these compounds. Using this cell mediated assay, we obtained mutagenesis with the carcinogenic hydrocarbons 7,12-dimethylbenz(alpha)anthracene (DMBA), BP, 3-methylcholanthrene and 7-methylbenz(alpha)anthracene; the most potent carcinogen, DMBA, gave the highest frequency of mutations. The polycyclic hydrocarbons, pyrene and benz(alpha)anthracene, which are not carcinogenic were also not mutagenic. We have therefore demonstrated a relationship between the carcinogenecity of polycyclic hydrocarbons and their mutagenicity in mammalian cells, without having to isolate their reative metabolic intermediates. It should be possible to use in this system human cells from different organs and individuals to screen for environmental chemicals hazardous to humans which have to be metabolically activated.     

Synergy between systemic toxicity and genotoxicity: relevance to human cancer risk

The health risk manager and policy analyst must frequently make recommendations based upon incomplete toxicity data. This is a situation which is encountered in the evaluation of human carcinogenic risks as animal cancer bioassay results are often not available. In this study, in order to assess the relevance of other possible indicators of carcinogenic risks, we used the "chemical diversity approach" to estimate the magnitude of the human carcinogenic risk based upon Salmonella mutagenicity and systemic toxicity data of the "universe of chemicals" to which humans have the potential to be exposed. Analyses of the properties of 10,000 agents representative of the "universe of chemicals" suggest that chemicals that have genotoxic potentials as well as exhibiting greater systemic toxicity are more likely to be carcinogens than non-genotoxicants or agents that exhibit lesser toxicity. Since "genotoxic" carcinogenicity is a hallmark of recognized human carcinogens, these findings are relevant to human cancer risk assessment.     

Occupational health and safety risk assessment in hospitals: A case study using two-stage fuzzy multi-criteria approach

Occupational Health and Safety (OHS) is a basis to reduce occupational accidents in an acceptable level, and it covers employee health, safety, and welfare in the workplaces. Hospitals as the largest employer group in healthcare industry in Turkey face major hazards categorized as chemical, biological, physical, ergonomic, and psychosocial risks. Although Turkey demonstrates rapid economic growth, OHS practices have not been fully put into practice, and necessary attention has not been paid to the health industry. For this reason, this paper aims to assess risks for health staff, contribute for planning of health services, and enhance regulations. A case study was carried out in a leading hospital in Turkey using a two-stage fuzzy multi-criteria approach, which provides more consistency in decision-making process and gives an appropriate final rank of hazard types. Fuzzy Analytic Hierarchy Process (FAHP) is used in weighing five risk parameters, which are severity, occurrence, undetectability, sensitivity to maintenance non-execution, and sensitivity to personal protective equipment (PPE) non-utilization. The fuzzy VIKOR (FVIKOR) approach is then applied for prioritization of hazard types in each department of the hospital. On conclusion of the hazard control hierarchy, measures are overtaken for the hazards, and areas open for improvement are presented.     

Consideration of both genotoxic and nongenotoxic mechanisms in predicting carcinogenic potential

Bacterial and cell culture genotoxicity assays have proven to be valuable in the identification of DNA reactive carcinogens because mutational events that alter the activity or expression of growth control genes are a key step in carcinogenesis. The addition of metabolizing enzymes to these assays have expanded the ability to identify agents that require metabolic activation. However, chemical carcinogenesis is a complex process dependent on toxicokinetics and involving at least steps of initiation, promotion and progression. Identification of those carcinogens that are activated in a manner unique to the whole animal, such as 2,6-dinitrotoluene, require in vivo genotoxicity assays. There are many different classes of non-DNA reactive carcinogens ranging from the potent promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) that acts through a specific receptor, to compounds that alter growth control, such as phenobarbital. Many compounds, such as saccharin, appear to exhibit initiating, promotional and/or carcinogenic activity as events secondary to induced cytotoxicity and cell proliferation seen only at the chronic lifetime maximum tolerated doses mandated in rodent bioassays. Simple plus/minus vs. carcinogen/noncarcinogen comparisons used to validate the predictivity of bacterial and cell culture genotoxicity assays have revealed that a more comprehensive analysis will be required to account for the carcinogenicity of so many diverse chemical agents. Predictive assays and risk assessments for the numerous types of nongenotoxic carcinogens will require understanding of their mechanism of action, reasons for target organ and species specificity, and the quantitative dose-response relationships between endpoints such as induced cell proliferation and carcinogenic potential.     

Ty1 transposition induced by carcinogens in Saccharomyces cerevisiae yeast depends on mitochondrial function

The transposition of the Ty mobile genetic element of Saccharomyces cerevisiae is induced by carcinogens. While the molecular background of spontaneous Ty1 transposition is well understood, the detailed mechanism of carcinogen induced Ty1 transposition is not clear. We found that mitochondrial functions participate in the Ty induced transposition induced by carcinogens. Contrary to the parental rho(+) cells rho(-) mutants (spontaneous or induced by ethidium bromide) do not increase the rate of Ty1 transposition upon treatment with carcinogens. Preliminary results strongly suggest that the absence of oxidative phosphorylation in rho(-) mutants is the reason for the inhibited Ty transposition. The lack of carcinogen induced Ty1 transposition in rho(-) cells is not specific for a particular carcinogen and represents a general feature of different carcinogenic substances inducing rho(-). It is concluded that carcinogen induced Ty1 transposition depends on the functional state of mitochondria and cannot take place in cells with compromised mitochondrial function (rho(-)).     

Dietary constituents altering the responses to chemical carcinogens.

This paper deals with two categories of compounds having the capacity to inhibit the neoplastic effects of chemical carcinogens on the host. The first are inducers of increased microsomal mixed function oxidase activity. An increasing number of these inducers are being found in natural products. Cruciferous vegetables including brussels sprouts, cabbage, and cauliflower contain such compounds. Recently indole-3-acetonitrile, indole-3-carbinol and 3,3'-diindolylmethane have been identified as inducers in these three plants. Other naturally occurring inducers include flavones, safrole, isosafrole, beta-ionone, and oxidized sterols. Since previous work has shown that synthetic inducers may protect against chemical carcinogens, the composition of the diet could play a role in inhibiting the neoplastic response to these carcinogenic agents. The second category of inhibitors comprises the antioxidants. Several of these compounds have been found to inhibit the carcinogenic effects of a variety of chemical carcinogens. Considerable work of this nature has been done with butylated hydroxyanisole and butylated hydroxytoluene two antioxidants extensively used as food additives. Other antioxidants having carcinogen inhibiting capacities include ethoxyquin, disulfiram, and dimethyldithiocarbamate.     

Study of uranium level in groundwater of Balod district of Chhattisgarh state,India and assessment of health risk

Uranium contamination in groundwater at Balod district of Chhattisgarh state was measured by laser fluorimetric technique. Most of the samples were found under safe limit for uranium contamination as recommended by WHO and USEPA (<30 µg l^?1) except Deur Tarai village (78.93 µg l^?1).The excess lifetime carcinogenic risk and chemical risk due to ingestion of groundwater were calculated using USEPA recommendations.     

DNA adducts in humans as dosimeters of exposure to environmental, occupational, or dietary genotoxins.

The quantitation of adducts of genotoxins with DNA is probably one of the best indicators of genetic damage due to exposure to toxins or carcinogens. It is generally believed that such adducts can lead to mutations, which in turn can trigger the initiation of the carcinogenic process. DNA adducts have been quantitated in white blood cells and in various tissues of smokers, persons in certain high-exposure occupations, and persons consuming foods contaminated with certain carcinogens. The feasibility of this approach for biochemical epidemiologic studies has been demonstrated using methods such as 32P-postlabeling, enzyme-linked immunosorbent assay, and synchronous fluorescence spectrophotometry. Relatively large interindividual differences in DNA adducts have been observed in both exposed and nonexposed persons. As a result, there are only a few studies in which clear quantitative and qualitative differences between these two groups have been observed. In addition, it appears that in some studies the 32P-postlabeling method does not detect the presence of the polycyclic aromatic hydrocarbon DNA adducts that are detectable by immunoassays. More extensive studies in additional populations at risk should shed further light on the utility of DNA adduct analysis in biochemical monitoring, especially if further refinements in methodology would result in increased sensitivity and specificity.     

Health risk assessment due to exposure of arsenic contamination in drinking water of district Shiekhupura,Punjab, Pakistan

Abstract

The present study was conducted to assess the magnitude and health impacts of As in drinking water. Drinking water samples (n?=?60) were collected from twenty different sites of Shiekhupura District (Pakistan). Health risk assessment through average daily dose (ADD), hazard indices (HI), hazard quotient (HQ), carcinogenic risk (CR), and cancer indices (CI) for dermal and oral exposure were determined. Results revealed that As concentration ranged from 2 to 900?µg?L^?1 in water samples, which was significantly greater than the safe limit of As (10?µg?L^?1) in water. Health risk assessment of As showed that ADD (1.07E?02–9.85E?04), HQ (1.06E+01–9.85E+00), and CR (1.60E?02–9.85E?04) for oral exposure and ADD (1.03E?05–9.69E?06), HQ (1.19E?02–7.96E?03), and CR (1.11E?05–8.98E?05) for dermal exposure which were exceeded the toxic risk index value. Comparison of the two exposure pathways indicated that the oral exposure is much higher risk than the dermal contact. Both values of HI and CI were greater than WHO limit. It is concluded that residents of study area are at higher risk of As induced diseases and carcinogenicity.     

Acrylamide: its metabolism, developmental and reproductive effects, genotoxicity, and carcinogenicity

Monomeric acrylamide is an important industrial chemical primarily used in the production of polymers and copolymers. It is also used for producing grouts and soil stabilizers. Acrylamide's neurotoxic properties have been well documented. This review will focus on pertinent information concerning other, non-neurotoxic, effects observed after exposure to acrylamide, including: its genotoxic, carcinogenic, reproductive, and developmental effects. It will also cover its absorption, metabolism, and distribution. The data show that acrylamide is capable of inducing genotoxic, carcinogenic, developmental, and reproductive effects in tested organisms. Thus, acrylamide may pose more than a neurotoxic health hazard to exposed humans. Acrylamide is a small organic molecule with very high water solubility. These properties probably facilitate its rapid absorption and distribution throughout the body. After absorption, acrylamide is rapidly metabolized, primarily by glutathione conjugation, and the majority of applied material is excreted within 24 h. Preferential bioconcentration of acrylamide and/or its metabolites is not observed although it appears to persist in tests and skin. Acrylamide can bind to DNA, presumably via a Michael addition-type reaction, which has implications for its genotoxic and carcinogenic potential. The available evidence suggests that acrylamide does not produce detectable gene mutations, but that the major concern for its genotoxicity is its clastogenic activity. This clastogenic activity has been observed in germinal tissues which suggest the possible heritability of acrylamide-induced DNA alterations. Since there is 'sufficient evidence' of carcinogenicity in experimental animals as outlined under the U.S. EPA proposed guidelines for carcinogen risk assessment, acrylamide should be categorized as a 'B2' carcinogen and therefore be considered a 'probable human carcinogen.' The very limited human epidemiological data do not provide sufficient evidence to enable one to judge the actual carcinogenic risk to humans. Acrylamide is able to cross the placenta, reach significant concentrations in the conceptus and produce direct developmental and post-natal effects in rodent offspring. It appears that acrylamide may produce neurotoxic effects in neonates from exposures not overtly toxic to the mothers. Acrylamide has an adverse effect on reproduction as evidenced by dominant lethal effects, degeneration of testicular epithelial tissue, and sperm-head abnormalities.     

Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma

Ionizing radiation is a well-known carcinogen, but its potency may be influenced by other environmental carcinogens, which is of practical importance in the assessment of risk. Data are scarce, however, on the combined effect of radiation with other environmental carcinogens and the underlying mechanisms involved. We studied the mode and mechanism of the carcinogenic effect of radiation in combination with N-ethyl-N-nitrosourea (ENU) using doses approximately equal to the corresponding thresholds. B6C3F1 mice exposed to fractionated X-irradiation (Kaplan's method) followed by ENU developed T-cell lymphomas in a dose-dependent manner. Radiation doses above an apparent threshold acted synergistically with ENU to promote lymphoma development, whereas radiation doses below that threshold antagonized lymphoma development. Ikaros, which regulates the commitment and differentiation of lymphoid lineage cells, is a critical tumor suppressor gene frequently altered in both human and mouse lymphomas and shows distinct mutation spectra between X-ray- and ENU-induced lymphomas. In the synergistically induced lymphomas, we observed a low frequency of LOH and an inordinate increase of Ikaros base substitutions characteristic of ENU-indcued point mutations, G:C to A:T at non-CpG, A:T to G:C, G:C to T:A and A:T to T:A. This suggests that radiation doses above an apparent threshold activate the ENU mutagenic pathway. This is the first report on the carcinogenic mechanism elicited by combined exposure to carcinogens below and above threshold doses based on the mutation spectrum of the causative gene. These findings constitute a basis for assessing human cancer risk following exposure to multiple carcinogens.     

Evaluation of a new model to detect bladder carcinogens or co-carcinogens; results obtained with saccharin, cyclamate and cyclophosphamide.

A sensitive rat model has been designed to detect potential weak bladder carcinogens or co-carcinogens. The test compound is given to animals which have received a single initiating, but non-carcinogenic, dose of N-methyl-N-nitrosourea (MNU). The model has been used to investigate two compounds currently under suspicion as weak bladder carcinogens, namely sodium saccharin and sodium cyclamate, and one compound known to be cytotoxic but not carcinogenic for the bladder epithelium namely cyclophosphamide. For comparison, these three compounds were also tested as solitary carcinogens in animals not pre-treated with MNU. At the very high dose levels used, sodium saccharin and sodium cyclamate were weak solitary carcinogens producing 4/253 and 3/228 bladder tumours respectively, and the first of these tumours did not appear for more than 80 weeks. When tested in the MNU/rat model more than half the animals receiving either sodium saccharin or sodium cyclamate developed bladder tumours from 10 weeks onwards. By contrast, cyclophosphamide failed to produce any tumours when tested either as a solitary carcinogen or in the MNU/rat model. It must be emphasized that the doses of saccharin and cyclamate used were far higher than those consumed by man, including diabetics, and these results should not be directly extrapolated to man without careful consideration of many other factors including negative epidemiological findings. The theoretical basis of the model is discussed and also the relevance, in terms of environmental human exposure, of detecting compounds which have a synergistic effect with other known bladder carcinogens. It appears that this model can be used to detect a carcinogenic or co-carcinogenic potential in compounds which are organotropic for the bladder more rapidly and with fewer animals than if the compounds are tested as solitary carcinogens by more conventional methods. It is suggested that it could be used to detect those compounds which require further investigation.     

A hybrid risk-based approach for maritime applications: The case of ballast tank maintenance

Risk assessment is vital for cost-effective ship management in maritime industry since numerous maritime activities pose potential hazards according to the human causalities. Therefore, safety practitioners attempt to offer proactive approaches to mitigate risk as much as possible. In this context, this article presents a hybrid risk-based approach for maritime industry by adopting Fuzzy Analytic Hierarchy Process (FAHP) with fuzzy VIKOR (FVIKOR) methods under Fine-Kinney approach. To illustrate the hybrid risk-based approach, ballast tank maintenance process is handled since there are various hazards causing fatalities, severe injuries, and illness during ballast tank maintenance procedure than any other type of shipboard work. An extensive risk analysis is performed to enhance environment safety and operational reliability in maritime industry. Besides its theoretical contribution, the outcomes of the paper contribute to improve overall safety level of ship by considering potential hazards in risk management.