Acrylamide is an industrially produced chemical with known neurotoxic, reproductive toxin and carcinogenic effects. The carcinogenicity associated with acrylamide is mostly attributed to its metabolism by liver CYP2E1. However, studies investigating the effects of acrylamide on CYP2E1 enzyme are limited. In this study, it was aimed to investigate in vivo interaction of carcinogenic acrylamide on microsomal cytochrome P450 enzyme activities, and protein levels, and on cytosolic NQO1 and GST enzyme activities of rabbit liver, kidney and lung of acrylamide-treated rabbits. The in vivo protective effect of resveratrol, a phenolic compound, was also investigated on acrylamide toxicity. New Zealand male rabbits were treated with acrylamide and resveratrol, separately in different doses and conditions. Their combined effects were also investigated. CYP2E1-dependent p-Nitrophenol hydroxylase, NDMA N-demethylase and aniline 4-hydroxylase activities were found to be significantly increased in acrylamide-treated rabbit liver (1.80-3.0 fold) and kidney (1.6-fold). Rabbit liver and kidney CYP2E1 protein levels (determined by western blot analyisis) also increased approximately 2-fold due to acrylamide treatment. In rabbit liver, resveratrol was found significantly effective in decreasing both acrylamide-induced CYP2E1-dependent enzyme activities (approximately 1.5-1.80 fold) and CYP2E1 protein levels (approximately 1.5-1.70 fold). Additionally, resveratrol significantly decreased acrylamide-induced CYP2E1 protein level (2-2.5 fold) in rabbit kidney. However, no significant change was observed in rabbit lung CYP2E1-dependent enzyme activities and CYP2E1 protein levels due to acrylamide, resveratrol or their combined treatments. Furthermore, it was found that acrylamide treatment significantly increased CYP3A6-dependent erythromycin N-demethylase enzyme activity (1.85-fold) and CYP3A6 protein levels in rabbit liver (1.69-fold). No change was observed in CYP2B4-dependent benzphetamine N-demethylase enzyme activities of rabbit liver, kidney and lung by in vivo acrylamide, resveratrol or their combined treatments. Moreover, total GST and GST-Mu activities of rabbit kidney (1.5-fold, respectively) and total GST activity of rabbit lung (1.6-fold) were increased significantly only in resveratrol treated group. NQO1 enzyme activity of rabbit kidney was significantly increased by acrylamide treatment (1.6-fold). The results of the present study have demonstrated for the first time that acrylamide induces rabbit liver and kidney CYP2E1-dependent enzyme activities and CYP2E1 protein levels. The induction of CYP2E1 enzyme activity and protein level by acrylamide treatment can stimulate formation of other toxic compounds and procarcinogens metabolized by CYP2E1 which in turn further potentiates the risk of hepatotoxicity, mutagenicity and carcinogenicity. In the present study, it was also demonstrated for the first time that acrylamide treatment also increases CYP3A6 enzyme activity in rabbit liver which may lead to alterations in drug metabolism. The results of this study have also suggested that resveratrol may have protective effects on acrylamide induced toxicity / however, further in vivo studies are required to clarify the effect of resveratrol on both acrylamide-induced toxicity and anti-oxidant enzymes.

According to the REACH regulation chemicals produced or imported to the European Union need to be assessed to manage the risk of potential hazard to human health and the environment. An increasing number of chemicals in commerce prompts the need for utilizing faster and cheaper alternative methods for this assessment, such as quantitative structure-activity or property relationships (QSARs or QSPRs). QSARs and QSPRs are models that seek correlation between data on chemicals molecular structure and a specific activity or property, such as environmental fate characteristics and (eco)toxicological effects. The aim of this thesis was to evaluate and develop models for the hazard assessment of industrial chemicals and the exposure assessment of pharmaceuticals. In focus were the identification of chemicals potentially demonstrating carcinogenic (C), mutagenic (M), or reprotoxic (R) effects, and endocrine disruption, the importance of metabolism in hazard identification, and the understanding of adsorption of ionisable chemicals to sludge with implications to the fate of pharmaceuticals in waste water treatment plants (WWTPs). Also, issues related to QSARs including consensus modelling, applicability domain, and ionisation of input structures were addressed. The main findings presented herein are as follows: QSARs were successful in identifying almost all carcinogens and most mutagens but worse in predicting chemicals toxic to reproduction. Metabolic activation is a key event in the identification of potentially hazardous chemicals, particularly for chemicals demonstrating estrogen (E) and transthyretin (T) related alterations of the endocrine system, but also for mutagens. The accuracy of currently available metabolism simulators is rather low for industrial chemicals. However, when combined with QSARs, the tool was found useful in identifying chemicals that demonstrated E- and T- related effects in vivo. We recommend using a consensus approach in final judgement about a compound’s toxicity that is to combine QSAR derived data to reach a consensus prediction. That is particularly useful for models based on data of slightly different molecular events or species. QSAR models need to have well-defined applicability domains (AD) to ensure their reliability, which can be reached by e.g. the conformal prediction (CP) method. By providing confidence metrics CP allows a better control over predictive boundaries of QSAR models than other distance-based AD methods. Pharmaceuticals can interact with sewage sludge by different intermolecular forces for which also the ionisation state has an impact. Developed models showed that sorption of neutral and positively-charged pharmaceuticals was mainly hydrophobicity-driven but also impacted by Pi-Pi and dipole-dipole forces. In contrast, negatively-charged molecules predominantly interacted via covalent bonding and ion-ion, ion-dipole, and dipole-dipole forces. Using ionised structures in multivariate modelling of sorption to sludge did not improve the model performance for positively- and negatively charged species but we noted an improvement for neutral chemicals that may be due to a more correct description of zwitterions.   Overall, the results provided insights on the current weaknesses and strengths of QSAR approaches in hazard and exposure assessment of chemicals. QSARs have a great potential to serve as commonly used tools in hazard identification to predict various responses demanded in chemical safety assessment. In combination with other tools they can provide fundaments for integrated testing strategies that gather and generate information about compound’s toxicity and provide insights of its potential hazard. The obtained results also show that QSARs can be utilized for pattern recognition that facilitates a better understanding of phenomena related to fate of chemicals in WWTP. / Enligt kemikalielagstiftningen REACH måste kemikalier som produceras i eller importeras till Europeiska unionen riskbedömas avseende hälso- och miljöfara. Den ökande mängden kemikalier som används i samhället kräver snabbare och billigare alternativa riskbedömningsmetoder, såsom kvantitativa struktur-aktivitets- eller egenskapssamband (QSARs eller QSPRs). QSARs och QSPRs är datamodeller där samband söks korrelationer mellan data för kemikaliers struktur-relaterade egenskaper och t.ex. kemikaliers persistens eller (eko)toxiska effekter. Målet med den här avhandlingen var att utvärdera och utveckla modeller för riskbedömning av industri kemikalier och läkemedel för att studera hur QSARs/QSPRs kan förbättra riskbedömningsprocessen. Fokus i avhandlingen var utveckling av metoder för identifiering av potentiellt cancerframkallande (C), mutagena (M), eller reproduktionstoxiska (R) kemikalier, och endokrint aktiva kemikalier, att studera betydelsen av metabolism vid riskbedömning och att öka vår förståelse för joniserbara kemikaliers adsorption till avloppsslam. Avhandlingen behandlar även konsensusmodellering, beskrivning av modellers giltighet och betydelsen av jonisering för kemiska deskriptorer. De huvudsakliga resultaten som presenteras i avhandlingen är: QSAR-modeller identifierade nästan alla cancerframkallande ämnen och de flesta mutagener men var sämre på att identifiera reproduktionstoxiska kemikalier. Metabolisk aktivering är av stor betydelse vid identifikationen av potentiellt toxiska kemikalier, speciellt för kemikalier som påvisar östrogen- (E) och sköldkörtel-relaterade (T) förändringar av det endokrina systemet men även för mutagener. Träffsäkerheten för de tillgängliga metabolismsimulatorerna är ganska låg för industriella kemikalier men i kombination med QSARs så var verktyget användbart för identifikation av kemikalier som påvisade E- och T-relaterade effekter in vivo. Vi rekommenderar att använda konsensusmodellering vid in silico baserad bedömning av kemikaliers toxicitet, d.v.s. att skapa en sammanvägd förutsägelse baserat på flera QSAR-modeller. Det är speciellt användbart för modeller som baseras på data från delvis olika mekanismer eller arter. QSAR-modeller måste ha ett väldefinierat giltighetsområde (AD) för att garantera dess pålitlighet vilket kan uppnås med t.ex. conformal prediction (CP)-metoden. CP-metoden ger en bättre kontroll över prediktiva gränser hos QSAR-modeller än andra distansbaserade AD-metoder. Läkemedel kan interagera med avloppsslam genom olika intermolekylära krafter som även påverkas av joniseringstillståndet. Modellerna visade att adsorptionen av neutrala och positivt laddade läkemedel var huvudsakligen hydrofobicitetsdrivna men också påverkade av Pi-Pi- och dipol-dipol-krafter. Negativt laddade molekyler interagerade huvudsakligen med slam via kovalent bindning och jon-jon-, jon-dipol-, och dipol-dipol-krafter. Kemiska deskriptorer baserade på joniserade molekyler förbättrade inte prestandan för adsorptionsmodeller för positiva och negativa joner men vi noterade en förbättring av modeller för neutrala substanser som kan bero på en mer korrekt beskrivning av zwitterjoner. Sammanfattningsvis visade resultaten på QSAR-modellers styrkor och svagheter för användning som verkyg vid risk- och exponeringsbedömning av kemikalier. QSARs har stor potential för bred användning vid riskidentifiering och för att förutsäga en mängd olika responser som krävs vid riskbedömning av kemikalier. I kombination med andra verktyg kan QSARs förse oss med data för användning vid integrerade bedömningar där data sammanvägs från olika metoder. De erhållna resultaten visar också att QSARs kan användas för att bedöma och ge en bättre förståelse för kemikaliers öde i vattenreningsverk.

Includes bibliographical references. / 1 v. (various foliations) : ill. (some col) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1994

Arsenic is a naturally occurring toxic metal and its presence in food composites could be a potential risk to the health of both humans and animals. Arseniccontaminated groundwater is often used for food and animal consumption, irrigation of soils, which could potentially lead to arsenic entering the human food chain. Its side effects include multiple organ damage, cancers, heart disease, diabetes mellitus, hypertension, lung disease and peripheral vascular disease. Research investigations, epidemiologic surveys and total diet studies (market baskets) provide datasets, information and knowledge on arsenic content in foods. The determination of the concentration of arsenic in rice varieties is an active area of research. With the increasing capability to measure the concentration of arsenic in foods, there are volumes of varied and continuously generated datasets on arsenic in food groups. Visual analytics, which integrates techniques from information visualization and computational data analysis via interactive visual interfaces, presents an approach to enable data on arsenic concentrations to be visually represented. The goal of this doctoral research in Environmental Science is to address the need to provide visual analytical decision support tools on arsenic content in various foods with special emphasis on rice. The hypothesis of this doctoral thesis research is that software enabled visual representation and user interaction facilitated by visual interfaces will help discover hidden relationships between arsenic content and food categories. The specific objectives investigated were: (1) Provide insightful visual analytic views of compiled data on arsenic in food categories; (2) Categorize table ready foods by arsenic content; (3) Compare arsenic content in rice product categories and (4) Identify informative sentences on arsenic concentrations in rice. The overall research method is secondary data analyses using visual analytics techniques implemented through Tableau Software. Several datasets were utilized to conduct visual analytical representations of data on arsenic concentrations in foods. These consisted of (i) arsenic concentrations in 459 crop samples; (ii) arsenic concentrations in 328 table ready foods from multi-year total diet studies; (iii) estimates of daily inorganic arsenic intake for 49 food groups from multicountry total diet studies; (iv) arsenic content in rice product categories for 193 samples of rice and rice products; (v) 758 sentences extracted from PubMed abstracts on arsenic in rice. Several key insights were made in this doctoral research. The concentration of inorganic arsenic in instant rice was lower than those of other rice types. The concentration of Dimethylarsinic Acid (DMA) in wild rice, an aquatic grass, was notably lower than rice varieties (e.g. 0.0099 ppm versus 0.182 for a long grain white rice). The categorization of 328 table ready foods into 12 categories enhances the communication on arsenic concentrations. Outlier concentration of arsenic in rice were observed in views constructed for integrating data from four total diet studies. The 193 rice samples were grouped into two groups using a cut-off level of 3 mcg of inorganic arsenic per serving. The visual analytics views constructed allow users to specify cut-off levels desired. A total of 86 sentences from 53 PubMed abstracts were identified as informative for arsenic concentrations. The sentences enabled literature curation for arsenic concentration and additional supporting information such as location of the research. An informative sentence provided global “normal” range of 0.08 to 0.20 mg/kg for arsenic in rice. A visual analytics resource developed was a dashboard that facilitates the interaction with text and a connection to the knowledge base of the PubMed literature database. The research reported provides a foundation for additional investigations on visual analytics of data on arsenic concentrations in foods. Considering the massive and complex data associated with contaminants in foods, the development of visual analytics tools are needed to facilitate diverse human cognitive tasks. Visual analytics tools can provide integrated automated analysis; interaction with data; and data visualization critically needed to enhance decision making. Stakeholders that would benefit include consumers; food and health safety personnel; farmers; and food producers. Arsenic content of baby foods warrants attention because of the early life exposures that could have life time adverse health consequences. The action of microorganisms in the soil is associated with availability of arsenic species for uptake by plants. Genomic data on microbial communities presents wealth of data to identify mitigation strategies for arsenic uptake by plants. Arsenic metabolism pathways encoded in microbial genomes warrants further research. Visual analytics tasks could facilitate the discovery of biological processes for mitigating arsenic uptake from soil. The increasing availability of central resources on data from total diet studies and research investigations presents a need for personnel with diverse levels of skills in data management and analysis. Training workshops and courses on the foundations and applications of visual analytics can contribute to global workforce development in food safety and environmental health. Research investigations could determine learning gains accomplished through hardware and software for visual analytics. Finally, there is need to develop and evaluate informatics tools that have visual analytics capabilities in the domain of contaminants in foods. / Environmental Sciences / P. Phil. (Environmental Science)

Polycyclic (or polynuclear) aromatic hydrocarbons (PAHs) are environmental pollutants produced during the incomplete combustion of organic matter. Since many of these compounds have been shown to be mutagenic and/or carcinogenic, an investigation was initiated into determining the PAH content and mutagenicity of the ash that remains after sugar cane crop burning, and the soot deposited on toll booths by vehicle exhaust emissions. Due to the large amount of sugar cane farming in the Natal coastal region and that the favoured method of disposing unwanted leafy trash is crop burning, concern was expressed as to the nature of the residue that is formed. PAHs have been identified in the residues from combusted wood and straw and, due to their intrinsic similarity to sugar cane, it was considered that the burning of sugar cane could generate PAHs. It is well documented that vehicle exhaust emissions exhibit mutagenic properties and PAHs have been identified as the major contributors of this observed mutagenicity. Since a toll plaza is an area of high traffic density, it was considered to be an ideal location for an investigation into the build-up of particles emitted by the passing vehicles, and to study to what extent the operators are exposed to harmful compounds. In addition, this sample acted as a control, since the detection of PAHs and mutagenic activity in the soot would be an indication that the correct experimental techniques were being employed. Samples were collected on site. The sugar cane ash was collected off a field immediately after burning had taken place, and the soot was collected either by scraping the toll booth walls and surrounding areas or by wiping the surfaces with cotton wool swabs. The organic portion of the samples was separated from the inorganic and carbonaceous substances by extraction into a suitable solvent; the use of both acetone and dichloromethane was investigated. The extracts were divided into two portions - one was used for the analysis of PAHs and the other for determining mutagenic activity. Analysis for PAHs involved subjecting the extracts to a sample clean-up routine and the use of a number of analytical techniques to characterise the components. The mutagenic properties of the samples were investigated by means of two bacterial mutagenicity tests: the Salmonella typhimurium assay (the Ames test) and a new commercially available test kit, the SOS Chromotest. A number of PARs were identified in the extracts by means of reverse phase high performance liquid chromatography (HPLC) with both ultraviolet and fluorescence detection, the latter being the more sensitive method. Mutagenic activity was detected for both samples in the Ames test and for the toll booth soot in the SOS Chromotest, and this observed mutagenicity was attributed to the presence of the PAHs. / Thesis (M.Sc.)-University of Natal, Durban, 1992.

A rápida oxidação da matéria orgânica dos solos tropicais é mais uma evidência da grande vantagem do uso de biossólidos como condicionadores, capazes de melhorar as características físicas, químicas e biológicas do solo com grandes reflexos na produtividade agrícola. Portanto, o presente projeto objetivou averiguar o potencial genotóxico e cancerígeno dos lotes do Lodo de Estação de Tratamento de Esgoto (LETE) gerado em uma ETE prédefinida na região da bacia hidrográfica Piracicaba, Capivari e Jundiaí (PCJ1). Estes dados poderão fornecer subsídios para a avaliação do risco das populações humanas e o meio ambiente expostas ao LETE. Foram utilizados 140 ratos Wistar machos com 8 semanas de idade, expostos, via ração, a concentrações de 10.000 e 50.000ppm de LETE, durante 6 e 8 semanas, com os iniciadores DEN (N-dietilnitrosamina) e DMH (1,2- dimetilhidrazina), conforme citado nos respectivos protocolos (Figuras 4 e 5). A avaliação toxicológica do lodo de esgoto desenvolvida pelo Núcleo de Avaliação do Impacto Ambiental Sobre a Saúde Humana (TOXICAM), enfocou os parâmetros toxicológicos, como seu potencial genotóxico, pelos testes do cometa e micronúcleo em sangue periférico e medula óssea e carcinogenicidade pelos ensaios de FCA e FHA. Os dois ensaios foram divididos em 4 grupos (FCA- GI=Controle Negativo, GII=Controle Positivo/DMH III=10.000ppmLETE e GIV=50.000ppmLETE); (FHAGI= Controle Negativo, GII=Controle Positivo/DEN, GIII=10.000ppmLETE e GIV=50.000ppmLETE). Entretanto, na 3ª semana foi realizada hepatectomia parcial em todos os animais dos respectivos grupos do ensaio de FHA. No teste do cometa foram utilizados 10 animais como controle positivo (controle interno - MNU-N-metil-N-nitrosourea), e 10 animais como controle negativo nos respectivos ensaios (FCA e FHA). Os testes em questão indicaram que o LETE não promove aumento do número de criptas aberrantes no cólon, número e área de focos de hepatócitos alterados no fígado, lesões no DNA (cometa), e também, não houve aumento de forma significativa a frequência de micronúcleo nas células, conforme as tabelas a seguir: 2.1(G=III e IV); 3.1(G=IV); 4(G=,III e IV); 5(G=III,IV e V); 6(G=III,IV e V); 7(G=IV e V). Em relação ao controle positivo. Estes dados poderão fornecer suporte na avaliação de risco da população humana e o meio ambiente, quando expostos ao lodo de estação de tratamento de esgoto. / Fast oxidation of organic matter on tropical soils is another evidence of the great advantage of using biosolids as conditioners once they are able to improve biological, chemical and physical characteristics of the soil with remarkable consequences on agricultural productivity. Therefore, the present project aimed at verifying genotoxic and carcinogenic potential plots of sludge from sewage treatment plants in a pre-defined watershed region at Piracicaba, Capivari and Jundiaí (PCJ1). These data may provide support to evaluate risks on human populations and the environment exposed to sludge from sewage treatment plants. In the study, 140 Wistar male rats, 8 weekold, were used. They were exposed, via chow, to a 10.000 and 50.000 ppm concentration of sludge from sewage treatment plants during 6 to 8 weeks with DEN initiators (diethylnitrosamine) and DMH (1,2-dimethylhydrazine) as mentioned in protocols (Figures 4 and 5). Toxicological evaluation of LETE developed by Center of Evaluation of Environmental Impact on Human Health (TOXICAM) focused toxicological parameters with its genotoxic potential by comet and micronucleus assays on peripheral blood and bone marrow in Wistar rats and carcinogenicity using ACF and AHF assays. Both assays were divided into 4 groups (ACF- GI=Negative Control, GII=Positive Control/DMH III=10.000ppmLETE and GIV=50.000ppmLETE); (AHF-GI=Negative Control, GII=Positive Positive/DEN, GIII=10.000ppmLETE and GIV=50.000ppmLETE). Therefore, on the 3rd week partial hepatectomy was performed in every animal from AHF assays respective groups. assays and to FCA comet test, using MNU (N-methyl-N-nitrosourea) as positive control. The tests in question indicated that the SS not promote increased number of aberrant crypts in the colon, number and area of foci of altered hepatocytes in the liver, lesions in DNA (comet), and also, significantly increased the frequency of micronucleus in cells, according to the following tables 2.1(G=III and IV); 3.1(G=IV); 4(G=,III and IV); 5(G=III,IV and V); 6(G=III,IV and V); 7(G=IV and V). For the positive control. These data may provide support to evaluate risks on human populations and the environment exposed to sludge from sewage treatment plants.

Les composés perfluorés (PFC) de formule chimique générale CF3-(CF2)n-SO3- ( sulfonates) ou CF3-(CF2)n-1-CO2- (acides) sont des polluants organiques émergents, dont la persistance, la bioaccumulation et la toxicité sont maintenant considérées préoccupantes au plan sanitaire et environnemental. L'objectif de notre recherche a été de mettre en évidence les effets cancérogènes in vitro et le mécanisme d'action impliqué lors de l'exposition pendant 7 jours de cellules embryonnaires de hamster Syrien (SHE) aux principaux représentants perfluorés, le sulfonate de perfluorooctane (PFOS), le perfluorooctanoate (PFOA), et à leur substitut, le sulfonate de perfluorobutane (PFBS). Le test de transformation cellulaire dans sa version standard ou selon un protocole de type initiation-promotion a permis de détecter les substances cancérogènes de profil initiateur ou promoteur de tumeur. La génotoxicité des PFCs a été explorée par le test Comet en conditions alcalines. PFOS a présenté un profil cancérogène non génotoxique de type initiateur aux concentrations de 0,37 et 3,7 µM (p<=0,01), coïncidant avec les concentrations sériques des travailleurs exposés au PFOS. L'activation des gènes PPARs a été observée après 7 jours d'exposition au PFOS, avec une induction plus importante et plus précoce (dès 24 heures d'exposition) du gène ppar-bêta/gamma aux concentrations transformantes (p<=0,05). PFOA appliqué seul n'induit pas la transformation néoplasique des cellules SHE. Par contre, il induit la transformation des cellules présensibilisées par un initiateur. Il agit selon un profil cancérogène non génotoxique de type promoteur de tumeur aux concentrations de 3,7 x 10-4 à 37 µM. Ces concentrations coïncident avec les concentrations sériques mesurées dans les populations professionnellement et non professionnellement exposées. PFBS ne s'est révélé ni initiateur, ni promoteur de tumeur. La mise en cause de ces PFCs dans l'augmentation des cancers de la vessie (pour le PFOS) et celui de la prostate (pour le PFOA) chez les travailleurs exposés ne peut être exclue / Perfluorinated compounds (PFCs) is a collective name for fluorinated surfactants and polymers with the general structure CF3-(CF2)n-SO3- (sulfonates) or CF3-(CF2)n-1-CO2- .(acids). This group is characterized by a high persistence, bioaccumulation and long term toxicity which are rising environmental and public health concerns. In the present work, we analyzed the in vitro carcinogenic potential of the two major PFCs, perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA), and their substitute, perfluorobutane sulfonate (PFBS). Cell transformation assays were carried out on Syrian hamster embryo (SHE) cells in a 7 day-treatment using the standard and the initiation-promotion protocols. Genotoxicity was tested using the comet assay. PFOS was not genotoxic on SHE cells, but it induced cell transformation at non cytotoxic concentrations 0,37 and 3,7 µM (p<=0,01). These concentrations coincided with serum PFOS concentrations measured in occupationally exposed workers. An increased expression of PPARs was registered after 7 days. The ppar-beta/gamma mRNA appeared to increase rapidly (24 hours after PFOS treatment) at concentrations closely related to cell transformation (p<=0,05). PFOA was inactive alone, but induced cell transformation of SHE cells pre-initiated with benzo(a)pyrene (BaP). Therefore PFOA was shown to act as a tumor promoter and a non genotoxic carcinogen at a large range of concentrations (3,7 x 10-4 à 37 µM). This range of concentrations covered seric concentrations in non-occupationally exposed and occupationally exposed populations. PFBS was negative alone and on BaP-pretreated SHE cells. For this reason, its use as a substitute for PFOS appears to be justified. To conclude, the cell transforming potenty of PFOS and PFOA denotes in vitro carcinogenic potential. Consequently, the hypothesis of their implication in human cancer recorded in occupationally exposed populations cannot be ruled out

A rápida oxidação da matéria orgânica dos solos tropicais é mais uma evidência da grande vantagem do uso de biossólidos como condicionadores, capazes de melhorar as características físicas, químicas e biológicas do solo com grandes reflexos na produtividade agrícola. Portanto, o presente projeto objetivou averiguar o potencial genotóxico e cancerígeno dos lotes do Lodo de Estação de Tratamento de Esgoto (LETE) gerado em uma ETE prédefinida na região da bacia hidrográfica Piracicaba, Capivari e Jundiaí (PCJ1). Estes dados poderão fornecer subsídios para a avaliação do risco das populações humanas e o meio ambiente expostas ao LETE. Foram utilizados 140 ratos Wistar machos com 8 semanas de idade, expostos, via ração, a concentrações de 10.000 e 50.000ppm de LETE, durante 6 e 8 semanas, com os iniciadores DEN (N-dietilnitrosamina) e DMH (1,2- dimetilhidrazina), conforme citado nos respectivos protocolos (Figuras 4 e 5). A avaliação toxicológica do lodo de esgoto desenvolvida pelo Núcleo de Avaliação do Impacto Ambiental Sobre a Saúde Humana (TOXICAM), enfocou os parâmetros toxicológicos, como seu potencial genotóxico, pelos testes do cometa e micronúcleo em sangue periférico e medula óssea e carcinogenicidade pelos ensaios de FCA e FHA. Os dois ensaios foram divididos em 4 grupos (FCA- GI=Controle Negativo, GII=Controle Positivo/DMH III=10.000ppmLETE e GIV=50.000ppmLETE); (FHAGI= Controle Negativo, GII=Controle Positivo/DEN, GIII=10.000ppmLETE e GIV=50.000ppmLETE). Entretanto, na 3ª semana foi realizada hepatectomia parcial em todos os animais dos respectivos grupos do ensaio de FHA. No teste do cometa foram utilizados 10 animais como controle positivo (controle interno - MNU-N-metil-N-nitrosourea), e 10 animais como controle negativo nos respectivos ensaios (FCA e FHA). Os testes em questão indicaram que o LETE não promove aumento do número de criptas aberrantes no cólon, número e área de focos de hepatócitos alterados no fígado, lesões no DNA (cometa), e também, não houve aumento de forma significativa a frequência de micronúcleo nas células, conforme as tabelas a seguir: 2.1(G=III e IV); 3.1(G=IV); 4(G=,III e IV); 5(G=III,IV e V); 6(G=III,IV e V); 7(G=IV e V). Em relação ao controle positivo. Estes dados poderão fornecer suporte na avaliação de risco da população humana e o meio ambiente, quando expostos ao lodo de estação de tratamento de esgoto. / Fast oxidation of organic matter on tropical soils is another evidence of the great advantage of using biosolids as conditioners once they are able to improve biological, chemical and physical characteristics of the soil with remarkable consequences on agricultural productivity. Therefore, the present project aimed at verifying genotoxic and carcinogenic potential plots of sludge from sewage treatment plants in a pre-defined watershed region at Piracicaba, Capivari and Jundiaí (PCJ1). These data may provide support to evaluate risks on human populations and the environment exposed to sludge from sewage treatment plants. In the study, 140 Wistar male rats, 8 weekold, were used. They were exposed, via chow, to a 10.000 and 50.000 ppm concentration of sludge from sewage treatment plants during 6 to 8 weeks with DEN initiators (diethylnitrosamine) and DMH (1,2-dimethylhydrazine) as mentioned in protocols (Figures 4 and 5). Toxicological evaluation of LETE developed by Center of Evaluation of Environmental Impact on Human Health (TOXICAM) focused toxicological parameters with its genotoxic potential by comet and micronucleus assays on peripheral blood and bone marrow in Wistar rats and carcinogenicity using ACF and AHF assays. Both assays were divided into 4 groups (ACF- GI=Negative Control, GII=Positive Control/DMH III=10.000ppmLETE and GIV=50.000ppmLETE); (AHF-GI=Negative Control, GII=Positive Positive/DEN, GIII=10.000ppmLETE and GIV=50.000ppmLETE). Therefore, on the 3rd week partial hepatectomy was performed in every animal from AHF assays respective groups. assays and to FCA comet test, using MNU (N-methyl-N-nitrosourea) as positive control. The tests in question indicated that the SS not promote increased number of aberrant crypts in the colon, number and area of foci of altered hepatocytes in the liver, lesions in DNA (comet), and also, significantly increased the frequency of micronucleus in cells, according to the following tables 2.1(G=III and IV); 3.1(G=IV); 4(G=,III and IV); 5(G=III,IV and V); 6(G=III,IV and V); 7(G=IV and V). For the positive control. These data may provide support to evaluate risks on human populations and the environment exposed to sludge from sewage treatment plants.

Arsenic is a naturally occurring toxic metal and its presence in food composites could be a potential risk to the health of both humans and animals. Arseniccontaminated groundwater is often used for food and animal consumption, irrigation of soils, which could potentially lead to arsenic entering the human food chain. Its side effects include multiple organ damage, cancers, heart disease, diabetes mellitus, hypertension, lung disease and peripheral vascular disease. Research investigations, epidemiologic surveys and total diet studies (market baskets) provide datasets, information and knowledge on arsenic content in foods. The determination of the concentration of arsenic in rice varieties is an active area of research. With the increasing capability to measure the concentration of arsenic in foods, there are volumes of varied and continuously generated datasets on arsenic in food groups. Visual analytics, which integrates techniques from information visualization and computational data analysis via interactive visual interfaces, presents an approach to enable data on arsenic concentrations to be visually represented. The goal of this doctoral research in Environmental Science is to address the need to provide visual analytical decision support tools on arsenic content in various foods with special emphasis on rice. The hypothesis of this doctoral thesis research is that software enabled visual representation and user interaction facilitated by visual interfaces will help discover hidden relationships between arsenic content and food categories. The specific objectives investigated were: (1) Provide insightful visual analytic views of compiled data on arsenic in food categories; (2) Categorize table ready foods by arsenic content; (3) Compare arsenic content in rice product categories and (4) Identify informative sentences on arsenic concentrations in rice. The overall research method is secondary data analyses using visual analytics techniques implemented through Tableau Software. Several datasets were utilized to conduct visual analytical representations of data on arsenic concentrations in foods. These consisted of (i) arsenic concentrations in 459 crop samples; (ii) arsenic concentrations in 328 table ready foods from multi-year total diet studies; (iii) estimates of daily inorganic arsenic intake for 49 food groups from multicountry total diet studies; (iv) arsenic content in rice product categories for 193 samples of rice and rice products; (v) 758 sentences extracted from PubMed abstracts on arsenic in rice. Several key insights were made in this doctoral research. The concentration of inorganic arsenic in instant rice was lower than those of other rice types. The concentration of Dimethylarsinic Acid (DMA) in wild rice, an aquatic grass, was notably lower than rice varieties (e.g. 0.0099 ppm versus 0.182 for a long grain white rice). The categorization of 328 table ready foods into 12 categories enhances the communication on arsenic concentrations. Outlier concentration of arsenic in rice were observed in views constructed for integrating data from four total diet studies. The 193 rice samples were grouped into two groups using a cut-off level of 3 mcg of inorganic arsenic per serving. The visual analytics views constructed allow users to specify cut-off levels desired. A total of 86 sentences from 53 PubMed abstracts were identified as informative for arsenic concentrations. The sentences enabled literature curation for arsenic concentration and additional supporting information such as location of the research. An informative sentence provided global “normal” range of 0.08 to 0.20 mg/kg for arsenic in rice. A visual analytics resource developed was a dashboard that facilitates the interaction with text and a connection to the knowledge base of the PubMed literature database. The research reported provides a foundation for additional investigations on visual analytics of data on arsenic concentrations in foods. Considering the massive and complex data associated with contaminants in foods, the development of visual analytics tools are needed to facilitate diverse human cognitive tasks. Visual analytics tools can provide integrated automated analysis; interaction with data; and data visualization critically needed to enhance decision making. Stakeholders that would benefit include consumers; food and health safety personnel; farmers; and food producers. Arsenic content of baby foods warrants attention because of the early life exposures that could have life time adverse health consequences. The action of microorganisms in the soil is associated with availability of arsenic species for uptake by plants. Genomic data on microbial communities presents wealth of data to identify mitigation strategies for arsenic uptake by plants. Arsenic metabolism pathways encoded in microbial genomes warrants further research. Visual analytics tasks could facilitate the discovery of biological processes for mitigating arsenic uptake from soil. The increasing availability of central resources on data from total diet studies and research investigations presents a need for personnel with diverse levels of skills in data management and analysis. Training workshops and courses on the foundations and applications of visual analytics can contribute to global workforce development in food safety and environmental health. Research investigations could determine learning gains accomplished through hardware and software for visual analytics. Finally, there is need to develop and evaluate informatics tools that have visual analytics capabilities in the domain of contaminants in foods. / Environmental Sciences / P. Phil. (Environmental Science)

The role of meat consumption in the development of cancer, including colorectal cancer (CRC), has been subject of much investigation in recent years. The observation of geographical variation in CRC incidence and increased CRC risks in populations consuming high levels of meat prompted researchers to hypothesise a link between meat and CRC. An area of particular interest in CRC pathogenesis is the meat-derived compounds such are heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and meatderived mutagenic activity. Australia is among the countries with high incidence of CRC and also high levels of per capita meat consumption. Hence, clarifying the possible link between meat consumption and the risk of CRC in order that this can be translated into preventive dietary recommendations for the public is important. The objective of this thesis was to examine whether meat consumption is related to risk of CRC in an Australian population. The term meat consumption in this thesis means meaures of consumption of red and white meat that incorporate frequency and cooking method. The following hypotheses were investigated: 1. Increasing intake of meat prepared by methods that involve higher cooking temperature and time is positively associated with the risk of CRC; 2. Increasing exposure to meat-derived heterocyclic amines (HCAs) is positively associated with the risk of CRC; 3. Higher levels of exposure to polycyclic aromatic hydrocarbons (PAHs) from meat consumption is a risk factor for CRC; 4. Exposure to meat-derived mutagens increases the risk of CRC.