Surfactants are one of the more ubiquitous contaminants in aquatic systems. Their importance as toxic components of pesticide formulations has, however, been largely overlooked. Amphibians particularly, as inhabitants of shallow, temporary and often lentic aquatic environments may be at risk from exposure to these chemicals when they enter aquatic systems. This thesis presents data on the toxicity of surfactants to amphibians. Several experimental exposures were conducted with embryo-larval, tadpole and adult developmental stages of the Australian species- Crinia insignifera, Helcioporus eyrei, Limnodynastes dorsalis and Litoria moorei and the exotic species- Bufo marinus and Xenopus laevis. Animals were variously exposed to glyphosate formulations that contain a high proportion of nonionic surfactants, or commercial pesticide wetting agents (alcohol alkoxylate and nonylphenol ethoxylate (NPE) surfactants). Feeding stage tadpoles of C.insignifera, H. eyrei, L. dorsalis and L. moorei were exposed to three commercial glyphosate formulations, glyphosate isopropylamine and glyphosate acid in static-renewal acute toxicity tests. The 48-h LC50 values for Roundup Herbicide (MON 2139) tested against tadpoles of C. insignifera, H. eyrei, L. dorsalis and L. moorei ranged between 8.1 and 32.2 mg/L (2.9 and 11.6 mg/L glyphosate acid equivalent (ae)), while the 48-h LC50 values for Roundup Herbicide tested against adult and newly metamorphosed C. insignifera ranged from 137-144 mg/L (49.4-51.8 mg/L ae). / Touchdown Herbicide (4 LC-E) tested against tadpoles of C. insignifera, H. eyrei, L. dorsalis and L. moorei was slightly less toxic than Roundup with 48-h LC50 values ranging between 27.3 and 48.7 mg/L (9.0 and 16.1 mg/L ae). Roundup Biactive (MON 77920) was practically non-toxic to tadpoles of the same four species producing 48-h LC50 values of 911 mg/L (328 mg/L ae) for L. moorei and >1000 mg/L (>360 mg/L ae) for C. insignifera, H. eyrei and L. dorsalis. Glyphosate isopropylamine was practically non-toxic producing no mortality amongst tadpoles of any of the four species over 48 h, at concentrations between 503 and 684 mg/L (343 and 466 mg/L ae). The toxicity of technical grade glyphosate acid (48-h LC50, 81.2-121 mg/L) is likely to be due to acid intolerance. Feeding stage tadpoles of B. marinus, X laevis, C. insignifera, H.eyrei, L. dorsalis and L. moorei were exposed to NPE and alcohol alkoxylate in static renewal acute toxicity tests. All species exhibited non-specific narcosis following exposure to both these surfactants. The 48-h EC50 values for NPE ranged between 1.1 mg/L (mild narcosis) and 12.1 mg/L (full narcosis). The 48-h EC50 values for alcohol alkoxylate ranged between 5.3 mg/L (mild narcosis) and 25.4 mg/L (full narcosis). Xenopus laevis was the most sensitive species tested. The sensitivity of the other five species was size dependent with larger species displaying greater tolerance. Replicate acute toxicity tests with B. marinus exposed to NPE at 30 degrees celsius over 96 hours indicated that the narcotic effects were not particularly time dependant. / The mean 24, 48, 72 and 96-h EC50 (mild narcosis) were 3.6, 3.7, 3.5 and 3.5 mg/L respectively. The mean 24, 48, 72, and 96-h EC50 (full narcosis) values were 4.0, 4.1, 4.2 and 4.0 respectively. Acute toxicity tests with B. marinus exposed to NPE at 30 degrees celsius under conditions of low dissolved oxygen (0.8-2.3 mg/L) produced a two to threefold increase in toxicity. The 12-h EC50 values ranged from 1.4 to 2.2 mg/L. The embryotoxicity of NPE was determined in X. laevis, L. adelaidensis and C. insignifera using a Frog Embryo Teratogenesis assay-Xenopus (FETAX). The 96-h LC50, EC50 and MCIG (LOEC) values for X. laevis were 3.9 to 5.4 mg/L, 2.8 to 4.6 mg/L and 1.0 to 3.0 mg/L respectively. The 140-h LC50, ECSO and MCIG values for L. adelaidensis were 9.2 mg/L, 8.8 mg/L and 5.1 to 6.0 ing/L respectively. The 134-h LC50, EC50 and MCIG values for C. insignifera were 6.4 mg/L, 4.5 mg/L and 4.0 mg/L respectively. Teratogenicity indices for the three species ranged between 1.0 and 1.6 indicating either no or low teratogenicity. Xenopus laevis was the more sensitive of the three species and the only species that displayed indisputable terata. The acute toxicity data indicated that the amphibian species tested were of similar sensitivity to fish and some invertebrates. Developmental retardation and oestrogenic effects following exposure to nonylphenol ethoxylate were indicated by sublethal toxicity tests. Crinia insignifera embryos were exposed during early embryogenesis to sublethal concentrations of NPE. / Exposure to NPE did not affect either weight nor size (snout-vent length) at metamorphosis. Exposure to 5.0mg/L NPE resulted in a significant delay in the time required to reach metamorphosis. Also, exposure to 3.0 mg/L NPE for the first 6 days of embryonic development or exposure to 5.0 mg/L NPE from day 2 to day 6 resulted in a statistically significant predominance in the female phenotype amongst metamorphosing froglets. Exposure for the first five days to 1.5 ing/L or 3.0 mg/L NPE had no effect on sex ratio. The results indicated that exposure to NPEs has endocrine disruptive effects in this species and that a narrow window of susceptibility exists for the induction of predominantly female phenotype. This study has also followed the degradation of a mixture of NPE oligomers and the concomitant formation of individual oligomers in static die-away tests with and without illumination in freshwater. Over 33 days in darkness there was a progressive and complete loss of long chain oligomers (NPEO(subscript)8-17), transient increases and subsequent loss of short to medium chain oligomers (NPE0(subscript)4-7), and large persistent increases (approximately 1000%) in short chain oligomers (NPE0(subscript)1-3). In the presence of illumination, biodegradation was retarded and heterotrophic bacterial proliferation was inhibited. After 33 days there was complete loss of long chain oligomers (NPE0(subscript)9-17), incomplete loss of medium chain oligomers (NPE0(subscript)6.8) and increases in short chain oligomers (NPE0(subscript)1-5). / This thesis discusses the importance of persistent metabolites of NPE degradation as it pertains to the habitat, developmental time frame and ecology of amphibians. Degradation of NPE is likely to occur over a time frame that is longer than that required for complete embryogenesis and metamorphosis of many species of amphibians, and may easily encompass those critical stages of development during which oestrogenic metabolites can affect development.

Existing ecotoxicity data for chemicals vary to a high extent between the environmental compartments water and sediment, since the evaluation of contaminants has historically focused on water exposition. Many anthropogenic chemicals and waste materials, including toxic organic and inorganic chemicals, adsorb to particulate matter and accumulate in sediments, and may thus be a threat to organisms living in the sediment. The invertebrates Chironomus riparius and Lumbriculus variegatus were selected as representatives of endobenthic living organisms. Acute toxicity tests, via water-only exposure, and sediment toxicity tests were conducted with the two endobenthic invertebrates. In sediment toxicity tests, organisms are mainly exposed to sediment- and particle-bound chemicals and dissolved chemical in the pore water. Toxicity data for algae, daphnids, and fish (via water-only exposure) are available for many substances, whereas the existing sediment toxicity data are rather rare. Thus, the interest arises to predict sediment toxicity for sediment-dwelling invertebrates from existing acute toxicity data of tests with water-only exposure. The main emphasis of this work was placed on one metal compound and seven organic chemicals. The objective of this study was fivefold: (1) develop methods and improve existing procedures on acute and sediment toxicity testing of the two invertebrates; (2) conduct both acute toxicity tests via water exposure and long-term sediment toxicity tests for the selected model substances to generate data for comparative discussion; (3) assess correlations among acute toxicity data of the organisms exposed via water-only and correlations among sediment toxicity data of the two endobenthic invertebrates for the eight tested chemicals; (4) assess possible forecasting for sediment toxicity from acute toxicity (via water-only exposure) and (5) assess exposure effects to determine the main exposure route. Acute toxicity data of the eight tested chemicals of D. magna significantly correlated with data of L. variegatus and C. riparius (p<0.05). However, a prediction of toxicity based on D. magna data bears high uncertainty, due to the small data set and high variation in sensitivity of the organisms. Existing sediment toxicity test methods were improved to meet the demand for artificial sediments containing organic matter that serves sufficiently as internal food source for the test organisms, and thus representing natural exposure conditions. However, the sediments that were used for the two organisms to test the selected model substances differed in sediment composition. Therefore, a sediment with the same sediment composition and the same water-to-sediment ratio for both invertebrates was developed, to have similar exposure conditions. In sediment toxicity tests, C. riparius was observed to be more sensitive than L. variegatus and no correlation was observed among data of the invertebrates. For the selected substances, lowest effect concentrations were observed for 3,4-dichloroaniline, whereas effect concentrations were the highest for benzo[a]pyrene. No correlations were found between the acute toxicity data of exposure via the water phase and sediment toxicity data, thus making a prediction of sediment toxicity data impossible. From analytical measurements of chemicals concentration in the compartments overlying, pore water, and bulk sediment, partition coefficients on sediment water partitioning were calculated. The highest partition coefficient ratios for sediment water partitioning were found for the high lipophilic organic substances 4,4-dichlorodiphenyltrichloroethan (DDT) and benzo[a]pyrene. Further, it was found that the main exposure routes in the 28-day sediment toxicity tests were not only chemical but species-dependent. As a result of very differing exposure routes for the tested chemicals and the absence of correlations from the acute to sediment toxicity data, sediment toxicity tests are necessary to assess the toxicity of chemicals on sediment inhabiting organisms. / In den meisten standardisierten ökotoxikologischen Untersuchungen zur Abschätzung des Gefährdungspotentials von Chemikalien für Gewässer erfolgt die Exposition der Organismen über die Wasserphase. Viele Schadstoffe, die in die aquatische Umwelt gelangen, adsorbieren aufgrund ihrer physikalisch-chemischen Eigenschaften an die Oberflächen von Schwebstoffen, sedimentieren und erreichen Sedimentkonzentrationen, die möglicherweise eine Gefahr für sedimentbewohnende Organismen darstellen. Im Rahmen dieser Arbeit wurden für benthische Invertebraten Testverfahren etabliert, bei denen eine Exposition der Organismen über das Sediment, hier hauptsächlich über die an ingestierte Sedimentbestandteile gebundene oder über die im Porenwasser gelöste Chemikalie (28-Tage Sedimenttoxizitätstest), und über dieWasserphase (Akuttoxizitätstest) erfolgte. Die Invertebraten Chironomus riparius und Lumbriculus variegatus wurden als typische Vertreter endobenthischer Organismen ausgewählt. Für viele Chemikalien liegen Daten zur akuten Toxizität für Algen, Daphnien und Fische für die Wasserexposition vor. Demgegenüber sind nur wenige Daten zur Toxizität für benthische Organismen weder mit einer Wasser- noch mit einer Sedimentexposition vorhanden. Als Modellsubstanzen wurden eine anorganische und sieben organische Substanzen für die Untersuchungen ausgewählt. Ziele dieser Arbeit waren: (1) die Entwicklung und Verbesserung von bestehenden Methoden zur Bestimmung der akuten Toxizität mitWasserexposition und der Sedimenttoxizität für die beiden Invertebraten; (2) die Durchführung der Tests mit den acht ausgewählten Modellsubstanzen zur vergleichenden Betrachtung; (3) die Beurteilung einer Korrelation der Daten zur Akuttoxizität innerhalb der verschiedenen Organismen mit Wasserexposition und einer Korrelation der Daten zwischen den beiden benthischen Organismen bei Sedimentexposition; (4) die Beurteilung einer Korrelation zwischen Daten der benthischen Invertebraten zur Akuttoxizität mit Wasserexposition und Sedimenttoxizität und (5) die Ermittlung und Bewertung der Expositionspfade. Die Akuttoxizitätsdaten von D. magna korrelieren significant (p<0.05) mit den Daten der beiden Invertebraten. Jedoch ist eine Vorhersage aufgrund des kleinen Datensatzes und der großen Unterschiede in der Empfindlichkeit der Arten abzulehnen. Um einer möglichst natürlichen Expositionssituation in Sedimenten zu entsprechen, wurden künstliche Sedimente mit interner Futterquelle, die auch mit der zu testenden Chemikalie kontaminiert wurde, entwickelt und für die Tests mit den Modellsubstanzen verwendet. Ein Nachteil war die unterschiedliche Sedimentzusammensetzung für die beiden Organismen. Um gleiche Expositionsbedingungen für beide Testorganismen zu gewährleisten, wurde ein artifizielles Sediment mit gleicher Zusammensetzung und gleichem Volumenverhältnis zwischen Sediment und Überstandswasser entwickelt. In den Sedimenttoxizitätstests reagierte C. riparius empfindlicher als L. variegatus. Die Effektkonzentrationen waren am niedrigsten für 3,4-Dichloraniline und am höchsten für Benzo[a]pyren. Die Korrelationen zwischen den Ergebnissen aus Akut- und Sedimenttoxizitstests waren nicht signifikant (p>0.05). Folglich läßt sich die Sedimenttoxizität nicht aus Daten zur akuten Toxizität mit Wasserexposition abschätzen. Aus den analytischen Messungen von Sediment-, Porenwasser- und Überstandswasserproben wurden die Koeffizienten für die Verteilung zwischen Sediment und Wasser berechnet. Für die stark lipophilen Stoffe, 4-Dichlorodiphenyltrichloroethan (DDT) und Benzo[a]pyren wurden die höchsten Koeffizienten errechnet. Weiterhin wurde festgestellt, daß die Hauptexpositionspfade in Sedimenttoxizitätstests einerseits von der Chemikalie und andererseits von der verwendeten Spezies abhängen. Aufgrund der Ergebnisse dieser Arbeit und der Tatsache, daß Sedimente “Senken” für viele Schadstoffe sind, müssen zur Erfassung und Bewertung des Gefährdungspotentials von Chemikalien gegenüber Sedimentbewohnern weiterhin Sedimenttoxizitätstests durchgeführt werden.

A contaminação de ambientes aquáticos decorrente de acidentes com gasolina, álcool combustível e misturas binárias representa um risco crescente, tendo em vista as projeções do setor para os próximos 50 anos. O objetivo do presente estudo foi avaliar a toxicidade aguda da Gasolina C, Gasolina P e álcool combustível isoladamente e em misturas binárias, assim como de suas respectivas Frações Solúveis em Água (FSA) e Frações Dispersas em Água (FDA) sobre Daphnia similis. O estudo ainda incluiu a avaliação da toxicidade aguda remanescente na matriz água de uma contaminação antiga (intemperismo) com a Gasolina C. Paralelamente, foram conduzidos ensaios de toxicidade aguda com amostras ambientais (água subterrânea, superficial e elutriato a partir de sedimentos) de uma área alagada com histórico de contaminação antiga. O cultivo e os ensaios com D. similis foram de acordo com a NBR 12.713 (2009). Tanto a gasolina C quanto a P foram extremamente tóxicas para os organismos, apresentando valores médios de CE50% em 48 h de 0,00113% e 0,058% respectivamente. As diferenças entre os resultados obtidos com a Gasolina C e aqueles obtidos com suas frações FSA e FDA foram significativas (p < 0,05), sendo que não houve diferença significativa entre a toxicidade aguda da FSA e da FDA (p < 0,05). Os resultados obtidos com os ensaios com Gasolina P e FDA não apresentaram diferenças significativas entre si (p < 0,05), mas, foram significativamente diferentes daqueles obtidos com FSA (p < 0,05). Os resultados dos ensaios de toxicidade aguda com misturas binárias sugeriram efeito menos que aditivo (antagonismo). Os resultados da simulação de uma contaminação antiga demonstraram redução acentuada da toxicidade para D. similis ao longo de apenas 28 dias. Entretanto, com relação aos ensaios com as amostras ambientais da área com histórico de contaminação, apesar da ausência ou baixa toxicidade nas amostras de água superficial (sugerindo intemperismo), toxicidade alta foi observada em amostras de água subterrânea e no elutriato de sedimentos, sugerindo condições de adsorção aos sedimentos com alto teor de argila e/ou aprisionamento dos compostos em zona saturada. / The contamination of aquatic environments due to accidents with gasoline, alcohol fuel and their mixtures represents an increasing risk due to the projections made by the petroleum-based fuels industry for the next 50 years. The objective of the present study was to assess the acute toxicity of gasoline C, gasoline P, ethanol fuel separately and in mixtures, as well as their respective water-soluble fractions (WSF) and water-disperse fraction (WDF) on the bioindicator Daphnia similis. The study also included the assessment of the remaining acute toxicity in an aged gasoline C-contaminated water matrix with aging simulation for a 28-day period. Parallel to that, toxicity assays were conducted with environmental samples, including surface water, elutriate of sediments and groundwater from an aged contaminated area. The cultivation and the assays with D. similis were carried out according to NBR 12.713 (2009). Both gasoline C and P were highly toxic to D. similis, with CE50% in 48 h of 0.00113% e 0.058% respectively. The differences in acute toxicity between Gasoline C and its fractions WSF and WDF were significant (p <0.05). However, no significant difference was found between WSF and WDF fractions. Gasoline P and its WDF fraction had no significant differences (p < 0.05), but their toxicity were significant different from that one obtained with the FSA fraction (p < 0.05). Acute toxicity assays carried out with gasoline C and P mixed with ethanol fuel suggested effect less than additive (antagonism). The results obtained with the simulation of an aged contamination with Gasoline C showed sharp reduction in toxicity along 28 days. However, regarding the assays with environmental samples from an aged contamination, although absence or low toxicity was observed in the superficial water, severe toxicity was found in the sediments elutriate and in the groundwater, which was confirmed by the high concentrations of gasoline hydrocarbons in both matrixes. The results suggest that the contaminant was entrapped in the saturated zone and/or adsorbed to the sediments with high clay content.

A contaminação de ambientes aquáticos decorrente de acidentes com gasolina, álcool combustível e misturas binárias representa um risco crescente, tendo em vista as projeções do setor para os próximos 50 anos. O objetivo do presente estudo foi avaliar a toxicidade aguda da Gasolina C, Gasolina P e álcool combustível isoladamente e em misturas binárias, assim como de suas respectivas Frações Solúveis em Água (FSA) e Frações Dispersas em Água (FDA) sobre Daphnia similis. O estudo ainda incluiu a avaliação da toxicidade aguda remanescente na matriz água de uma contaminação antiga (intemperismo) com a Gasolina C. Paralelamente, foram conduzidos ensaios de toxicidade aguda com amostras ambientais (água subterrânea, superficial e elutriato a partir de sedimentos) de uma área alagada com histórico de contaminação antiga. O cultivo e os ensaios com D. similis foram de acordo com a NBR 12.713 (2009). Tanto a gasolina C quanto a P foram extremamente tóxicas para os organismos, apresentando valores médios de CE50% em 48 h de 0,00113% e 0,058% respectivamente. As diferenças entre os resultados obtidos com a Gasolina C e aqueles obtidos com suas frações FSA e FDA foram significativas (p < 0,05), sendo que não houve diferença significativa entre a toxicidade aguda da FSA e da FDA (p < 0,05). Os resultados obtidos com os ensaios com Gasolina P e FDA não apresentaram diferenças significativas entre si (p < 0,05), mas, foram significativamente diferentes daqueles obtidos com FSA (p < 0,05). Os resultados dos ensaios de toxicidade aguda com misturas binárias sugeriram efeito menos que aditivo (antagonismo). Os resultados da simulação de uma contaminação antiga demonstraram redução acentuada da toxicidade para D. similis ao longo de apenas 28 dias. Entretanto, com relação aos ensaios com as amostras ambientais da área com histórico de contaminação, apesar da ausência ou baixa toxicidade nas amostras de água superficial (sugerindo intemperismo), toxicidade alta foi observada em amostras de água subterrânea e no elutriato de sedimentos, sugerindo condições de adsorção aos sedimentos com alto teor de argila e/ou aprisionamento dos compostos em zona saturada. / The contamination of aquatic environments due to accidents with gasoline, alcohol fuel and their mixtures represents an increasing risk due to the projections made by the petroleum-based fuels industry for the next 50 years. The objective of the present study was to assess the acute toxicity of gasoline C, gasoline P, ethanol fuel separately and in mixtures, as well as their respective water-soluble fractions (WSF) and water-disperse fraction (WDF) on the bioindicator Daphnia similis. The study also included the assessment of the remaining acute toxicity in an aged gasoline C-contaminated water matrix with aging simulation for a 28-day period. Parallel to that, toxicity assays were conducted with environmental samples, including surface water, elutriate of sediments and groundwater from an aged contaminated area. The cultivation and the assays with D. similis were carried out according to NBR 12.713 (2009). Both gasoline C and P were highly toxic to D. similis, with CE50% in 48 h of 0.00113% e 0.058% respectively. The differences in acute toxicity between Gasoline C and its fractions WSF and WDF were significant (p <0.05). However, no significant difference was found between WSF and WDF fractions. Gasoline P and its WDF fraction had no significant differences (p < 0.05), but their toxicity were significant different from that one obtained with the FSA fraction (p < 0.05). Acute toxicity assays carried out with gasoline C and P mixed with ethanol fuel suggested effect less than additive (antagonism). The results obtained with the simulation of an aged contamination with Gasoline C showed sharp reduction in toxicity along 28 days. However, regarding the assays with environmental samples from an aged contamination, although absence or low toxicity was observed in the superficial water, severe toxicity was found in the sediments elutriate and in the groundwater, which was confirmed by the high concentrations of gasoline hydrocarbons in both matrixes. The results suggest that the contaminant was entrapped in the saturated zone and/or adsorbed to the sediments with high clay content.

The species Vernonia tweedieana Baker is an herbaceous plant widely distributed in the plains of Paraguai, Argentina and south of Brazil and popularly known as assa-peixe . This plant is used in traditional medicine as an expectorant medicament. So far, this plant was not studied on the phytochemical and biological point of view. This work is a contribution to the phytochemical study of the Asteraceae. The leaves of V. tweedieana Baker were collected in march of 2004, in Ijuí Rio Grande do Sul, Brazil, and identified by Dr. Geraldo C. Coelho (UNIJUÍ). The respective voucher specimen was deposited in the herbarium of the Federal University of Santa Maria (UFSM)-RS (code SMDB 9536). The leaves (1.900 g) were dried in an air circulating stove at 40 ºC, pulverized in mill and extracted by maceration with 65% EtOH at room temperature for seven days. The ethanolic extract was filtered and the ethanol was removed. Finally, the extract was retake in water and partitioned using organics solvents with increased polarity: CH2Cl2, AcOEt and n-BuOH. We report the isolation and identification of six constituents of the CH2Cl2 fraction: the triterpenes a-amyrin, b-amyrin and lupeol and the steroids b- sitosterol, stigmasterol and spinasterol. The flavanone eriodictyoI was isolated from the AcOEt fraction. The constituents were identified through spectral data of the infra-red, GC-MS, 1H-NMR, 13C-NMR and DEPT. No deaths and other signs of toxicity and adverse effect were observed in the evaluation of acute toxicity with doses up to 5.000 mg/kg, that is the maximum dose for acute oral toxicity test for extract of plants. Also, through DPPH method, AcOEt and n-BuOH fractions of the plant showed good antioxidant activity with IC50 22.52 and 17.44 mg/mL, respectively. / O uso de plantas medicinais sempre teve uma importância vital no cotidiano da humanidade. No entanto, apenas uma pequena parte destas já foram estudadas e tiveram suas ações farmacológicas comprovadas cientificamente. Um exemplo de planta ainda desconhecida quimicamente é Vernonia tweedieana Baker (Asteraceae), vulgarmente conhecida como assa-peixe. É uma planta característica da região Sul do Brasil que é usada popularmente para o tratamento de doenças respiratórias, principalmente pelas suas propriedades expectorantes. Este trabalho descreve o isolamento e identificação de seis constituintes químicos presentes no extrato CH2Cl2 e de um no extrato AcOEt das folhas de Vernonia Tweedieana Baker. As folhas foram coletadas em março de 2004, no município de Ijuí RS. A espécie foi localizada e identificada pelo Prof. Dr. Geraldo C. Coelho (DeBQ-UNIJUÍ). Material testemunha encontra-se depositado no Herbário do Departamento de Biologia da UFSM sob o registro n° SMDB 9536. O material vegetal seco e moído (1.900 g) foi macerado utilizando como solvente etanol:água (65:35, v/v). Após sete dias o extrato foi filtrado e concentrado sob pressão reduzida para remover o etanol. Fez-se fracionamento desse extrato bruto com solventes orgânicos de polaridades crescentes (CH2Cl2, AcOEt, n- BuOH). Da fração CH2Cl2 caracterizou-se os triterpenos a e b-amirinas e lupeol, ainda os esteróides b-sitosterol, estigmasterol e espinasterol; e da fração AcOEt o flavonóide eriodictiol. Os compostos isolados foram analisados por CG-EM-IE, IV, RMN de 1H e RMN de 13C e seus dados espectroscópicos foram comparados com os obtidos da literatura. Ainda, na avaliação da toxicidade aguda foi verificado que nenhum dos extratos apresentou toxicidade em doses até 5.000 mg/mL. Também, pelo método do DPPH, foi constatada atividade antioxidante para as frações AcOEt e n-BuOH da planta, apresentando IC50 de 22,52 e 17, 44 mg/mL, respectivamente.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This present study is about the phytotherapic effects of the hydroalchoholic extracted from the Hyptis fruticosa leaves. Typical plant from the northeast of Brazil used as an aromatyzer and discongestyzer. Probably, de Araújo et. al., 1974, were the first ones to study and discribe the studies of the metanolic extracts from the roots of this plant, that contains antimicroorganism and antineoplasic activity. Pain, insomnia and epilepsy are disturbs that attack people in our society, specially pain, causing personal and socialeconomic problems. The main objective of this study is to describe partialy the effects of the hydroalchoholic extracted from the Hyptis fruticosa Salzm. (ex) Benth. leaves in the nervours central system of mice. Having as specifics objectives: to determinate the acute toxicity (DL50); to evidence the anticonvulsant and sedative/hypnotic effects; to mensure the antinociceptive effects in mice. This is an experimental search using acute toxicity test in the doses 1, 2, 3, 4 and 5 grams; pentylenetetrazole-induced convulsion, 60mg/Kg i.p.; pentobarbital-induced sleep, 60mg/Kg i.p.; writhing-induced by acetic acid 6% and tail-flick test. The animals used were the swiss type mice. The data obtained were analysed by ANOVA, the p<0,05 values were considered significant. According to the results, it was demonstrated that the estract has low toxicity; the pentylenetetrazole-induced convulsion showed a latence low increase for the beginning of the 1ª convulsion and the death; The ANOVA showed significance with p<0,0001 at the return of the righting reflex on the sleep-induced by tiopental, writhing-induced by acetic acid and thermal nociceptive stimulation. Is possible to conclude, this way, that the hydroalchoholic extract of Hyptis fruticosa leaves has antinociceptive effects on the central and peripheral nervous system and low sedative, however, without any anticonvulsant activity. For more informations, studies with more details is suggested. / O presente trabalho trata de um estudo sobre os efeitos fitoterápicos do extrato hidroalcoólico das folhas da Hyptis fruticosa. Planta típica do nordeste do Brasil utilizada como aromatizante e descongestionante, provavelmente, de Araújo e colaboradores, 1974, foram os primeiros a relatar estudo dos extratos metanólicos extraídos das raízes da planta, com atividade antimicrobiana e antineoplásica. A dor, a insônia e a epilepsia são transtornos que afligem as pessoas na sociedade, principalmente a dor, causando prejuízos pessoais e socioeconômicos. O objetivo principal deste estudo é caracterizar parcialmente os efeitos do extrato hidroalcoólico das folhas da Hyptis fruticosa Salzm. (ex) Benth. no sistema nervoso central de camundongos; tendo como objetivos específicos determinar a toxicidade aguda (DL50); evidenciar efeito convulsivante e sedativo/hipnótico; e mensurar efeitos antinociceptivos em camundongos. Essa pesquisa é do tipo experimental utilizando os teste de toxicidade aguda nas doses 1, 2, 3, 4 e 5 gramas; os testes de convulsão induzida por pentilenotetrazol, 60mg/Kg i.p., sono induzido por tiopental sódico, 60mg/Kg i.p., contorção abdominal induzida por ácido acético a 6% e teste Tail-flick . Os animais utilizados foram camundongos do tipo Swiss. Os dados obtidos foram analisados pela ANOVA, valores de p<0,05 foram considerados significativos. Em relação aos resultados foi demonstrado que o extrato é de baixa toxicidade. No teste de convulsão induzida por pentilenotetrazol houve pequeno aumento na latência para o início da 1ª convulsão e para a morte. Em relação a ANOVA nos testes quanto a recuperação do reflexo de endireitamento no sono induzido por tiopental, contorção abdominal por ácido acético e nocicepção térmica, os mesmos revelaram significância com p<0,0001. Conclui-se desta forma que o extrato das folhas da Hyptis fruticosa Salzm. (ex) Benth. apresenta efeito antinociceptivo no sistema nervoso central e Caracterização Parcial dos Efeitos do Extrato Hidroalcoólico... 9 periférico e pequena sedação, porém, sem nenhuma atividade anticonvulsivante. Sugere-se estudos mais detalhados para maiores esclarecimentos.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-12-08T07:46:47Z No. of bitstreams: 2 Dissertação - Letícia Freire de Oliveira - 2015.pdf: 1336117 bytes, checksum: d7d9a7965dc7492a12ce5fcb44c65555 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-12-08T07:48:34Z (GMT) No. of bitstreams: 2 Dissertação - Letícia Freire de Oliveira - 2015.pdf: 1336117 bytes, checksum: d7d9a7965dc7492a12ce5fcb44c65555 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-12-08T07:48:34Z (GMT). No. of bitstreams: 2 Dissertação - Letícia Freire de Oliveira - 2015.pdf: 1336117 bytes, checksum: d7d9a7965dc7492a12ce5fcb44c65555 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-04-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The peach palm is a native Palm from humid tropics of the Amazon, used for the production of palm raw or pickled, becoming an important alternative to reduction of predatory exploitation of other palms. The sheath, external, middle and internal, that involve the noble party, called palm or palmetto, are not used during the plicked of palm processing, yielding tons of waste, and the production of flour, is an excellent alternative to the use of these. This research, therefore, aimed the physical, chemical, technological and toxicological study, of the waste sheaths flour, external, middle and internal, peach palm (PF). The flour has a low moisture content (4.74%), proteins (5.03 g(100g)-1), lipids (2.12 g(100g)-1), soluble dietary fiber (3.40 g(100g)-1), ash (4.69 g(100g)-1) and high content of insoluble dietary fiber (49,53 g(100g)-1). Regarding water absorption, milk and oil, the flour had good absorption capacity. The flour showed low acidity (1.36%), clear and attractive coloring, and the particle size was presented between fine and very fine. It was noted, also, high amount of resistant starch (20%) and the presence of reducing sugars as fructose (6.70 g(100g)-1) and glucose (7.50 g(100g)-1). The most significant amino acid were glutamic acid (392.63 mg(100g)-1), arginine (363.76 mg(100g)-1), aspartic acid (348.93 mg(100g)-1). The PF and waste sheaths, external, middle and internal, fresh, of peach palm (WP) showed low amounts of phytic acid, condensed tannins and hydrolysates. The PF showed 100% of protein digestibility, and the lyophilized aqueous extract of waste sheaths flour, external, middle and internal of peach palm (PE), showed low toxicity. The results of this research suggest that the PF can be used in bakery products such as breads, cookies and cakes, besides the application in meat products, milk drinks, cheese, among others, contributing, nutritionally, in addition or partial replacement of flour wheat in processed foods, without to reduce the bioavailability of nutrients, representing too, toxicological safety, due to the absence of toxic compounds in PE. / A pupunheira é uma palmeira nativa dos trópicos úmidos da Amazônia, utilizada para a produção de palmito in natura ou em conserva, tornando-se uma importante alternativa para a redução da exploração predatória de outras palmeiras. As bainhas, externa, mediana e interna, que envolvem a parte nobre, denominada palmito, não são aproveitadas durante o processamento do palmito em conserva, gerando toneladas de resíduos, sendo, a produção de farinha, excelente alternativa para o aproveitamento desses. Este trabalho, portanto, teve como objetivo o estudo físico, químico, tecnológico e toxicológico, da farinha das bainhas residuais, externa, mediana e interna, da pupunha (FP). A farinha obtida possui baixo teor de umidade (4,74%), proteínas (5,03 g(100g)-1), lipídios (2,12 g(100g)-1), fibra alimentar solúvel (3,40 g(100g)-1), cinzas (4,69 g(100g)-1) e alta quantidade de fibra alimentar insolúvel (49,53 g(100g)-1). Em relação à absorção em água, leite e óleo, a farinha apresentou boa capacidade de absorção. A farinha apresentou baixa acidez (1,36%), coloração clara e atrativa, e a granulometria apresentou-se entre fina e muito fina. Notou-se, também, alta quantidade de amido resistente (20%) e a presença de açúcares redutores como, frutose (6,70 g(100g)-1) e glicose (7,50 g(100g)-1). Os aminoácidos mais expressivos foram o ácido glutâmico (392,63 mg(100g)-1) arginina (363,76 mg(100g)-1) e ácido aspártico (348,93 mg(100g)-1). A FP e as bainhas residuais, externas, medianas e internas, in natura, do palmito de pupunha (PN), apresentaram baixa quantidade de ácido fítico, taninos condensados e hidrolisados. A FP apresentou 100 % de digestibilidade de proteína, e o extrato aquoso liofilizado da farinha das bainhas residuais, externa, mediana e internas da pupunheira (EP), apresentou baixa toxicidade. Os resultados deste estudo sugerem que a FP pode ser empregada em produtos de panificação, como pães, biscoitos e bolos, além da aplicação em produtos cárneos, bebidas lácteas, queijos, entre outros, contribuindo, nutricionalmente, na adição ou substituição parcial à farinha de trigo, em alimentos industrializados, sem que haja redução da biodisponibilidade de nutrientes, representando também, segurança toxicológica, devido à ausência de compostos tóxicos no EP.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-11-24T12:08:05Z No. of bitstreams: 2 Dissertação - Renato Ivan de Ávila Marcelino - 2013.pdf: 1307159 bytes, checksum: 353b525742af80ec75afbd4c58f79c96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-11-24T14:01:41Z (GMT) No. of bitstreams: 2 Dissertação - Renato Ivan de Ávila Marcelino - 2013.pdf: 1307159 bytes, checksum: 353b525742af80ec75afbd4c58f79c96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-11-24T14:01:41Z (GMT). No. of bitstreams: 2 Dissertação - Renato Ivan de Ávila Marcelino - 2013.pdf: 1307159 bytes, checksum: 353b525742af80ec75afbd4c58f79c96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-04-19 / Hexavalent chromium [Cr(VI)] is a toxic metal that triggers toxicity events in the body, penetrating cell membranes and increasing reactive oxygen species (ROS). These products, in turn, damage cellular macromolecules, inhibiting their functions and enhancing cell death via apoptosis. Therefore, it has been suggested that the use of antioxidants can minimize the damage induced by this metal. In this context, the Eugenia dysenterica DC. (Myrtaceae) plant species, native from Cerrado biome, has been studied because it presents high levels of polyphenols, substances with known antioxidant potential. Moreover, it is traditionally used in folk medicine and presents food and economic importance. In this work, in vitro and in vivo effects of the Eugenia dysenterica DC. leaf hydroalcoholic extract (EDE) on AMJ2-C11 cell line and mice exposed to Cr(VI), respectively, were investigated. In parallel, the antioxidant activity of EDE was also investigated by the methods of 2,2-Diphenyl-1-picrylhydrazyl (DPPH•) free radical capturing and co-oxidation of β-caroteno/linoleic acid. In vitro, pre-treatment of AMJ2-C11 cells with EDE (20, 40 ou 80 μg/mL) followed by exposure to Cr(VI) (100, 250 ou 500 μM) resulted in a concentration-dependent increase of cell viability. Furthermore, mechanistic studies of flow cytometry (cell cycle, annexin V, active caspases, ROS and rhodamine 123) and cell morphology showed that the EDE protected the cells from apoptosis triggered by Cr(VI), and reduced the ROS intracellular levels and prevented the loss of mitochondrial membrane potential. Additionally, significant antioxidant potential of EDE was observed. In vivo, prophylactic treatment for 10 days with EDE (50, 100 ou 200 mg/kg/day) and subsequent exposure to a sublethal dose of Cr(VI) (30 mg/kg) induced a decrease in Cr levels in the kidneys, liver and plasm, besides preventing liver and kidney changes caused by this metal. Moreover, treatment of animals with EDE (50, 100, 125, 200, 250 ou 500 mg/kg/day) followed by exposure to a lethal dose of Cr(VI) (50 mg/kg) induced an increase in the survival of exposed animals, especially at the doses of 50, 100 and 125 mg/kg. Therefore, the present study demonstrated that the EDE showed in vitro and in vivo effect against Cr(VI)-induced oxidative toxicity. / O cromo hexavalente [Cr(VI)] é um metal tóxico capaz de desencadear eventos toxicológicos no organismo, pois ultrapassa as membranas celulares e promove o aumento da produção de espécies reativas de oxigênio (ERO). Esses produtos, por sua vez, danificam as macromoléculas celulares, inibindo suas funções e favorecendo a morte celular por apoptose. Em vista disso, acredita-se que o uso de antioxidantes pode minimizar os danos induzidos por este metal. Nesse contexto, a espécie vegetal Eugenia dysenterica DC. (Myrtaceae), nativa do bioma Cerrado, tem sido estudada por apresentar altos níveis de polifenóis, substâncias que reconhecidamente têm potencial antioxidante. Ademais, é tradicionalmente utilizada na medicina popular e apresenta importância alimentar e econômica. Assim, neste trabalho, os efeitos in vitro e in vivo do extrato hidroalcoólico das folhas da Eugenia dysenterica (EED) sobre a linhagem celular AMJ2-C11 e em camundongos expostos ao Cr(VI), respectivamente, foram investigados. Em paralelo, a atividade antioxidante do EED também foi investigada através dos métodos de captura do radical livre 2,2-difenil-1-picrilidrazila (DPPH•) e da co-oxidação do β-caroteno/ácido linoléico. In vitro, o pré-tratamento das células AMJ2-C11 com EED (20, 40 ou 80 μg/mL) seguido de exposição ao Cr(VI) (100, 250 ou 500 μM) resultou em um aumento da viabilidade celular, de forma concentração dependente. Além disso, estudos mecanísticos utilizando citômetro de fluxo (ciclo celular, anexina V, caspases ativas, ERO e rodamina 123) e de morfologia celular evidenciaram que o EED protegeu as células da apoptose desencadeada pelo Cr(VI), além de reduzir os níveis intracelulares de ERO e impedir a perda do potencial de membrana mitocondrial. Adicionalmente, foi observado relevante potencial antioxidante do EED. In vivo, o tratamento profilático por 10 dias com EED (50, 100 ou 200 mg/kg/dia) e subsequente exposição a uma dose subletal de Cr(VI) (30 mg/kg) promoveu redução dos níveis de Cr nos rins, fígado e plasma, além de prevenir alterações hepáticas e renais causadas por esse metal. Além disso, o tratamento dos animais com EED (50, 100, 125, 200, 250 ou 500 mg/kg/dia) seguido de exposição a uma dose letal de Cr(VI) (50 mg/kg) promoveu um aumento da sobrevida dos animais expostos, principalmente nas doses de 50, 100 e 125 mg/kg. Por conseguinte, o presente estudo demonstrou que o EED

Submitted by Marilene Donadel (marilene.donadel@unioeste.br) on 2018-04-26T18:38:37Z No. of bitstreams: 1 Karina_Sanderson_2017.pdf: 3684654 bytes, checksum: 61d1f7f0f704e49f62966d42bae3ceae (MD5) / Made available in DSpace on 2018-04-26T18:38:37Z (GMT). No. of bitstreams: 1 Karina_Sanderson_2017.pdf: 3684654 bytes, checksum: 61d1f7f0f704e49f62966d42bae3ceae (MD5) Previous issue date: 2017-12-13 / Power distribution companies constantly contaminate the environment with dielectric fluids due to power transformer failures and leaks. In this way, these fluids should be studied, as they may entail the vulnerability of the fauna and flora. In this sense, the objective of this work was to investigate the deleterious effects of vegetal and mineral dielectric fluids, through biodegradability, acute toxicity, chemical attributes and soil degradation (oils and greases) tests as well as soybean phytotechnical characteristics evaluation. In the tests of the immediate biodegradability, vegetal dielectric fluids of crambe, W3, W6 and W9 and one based on mineral oil (Lubrax) were studied. For the acute toxicity tests with Danio rerio and Artemia salina and the soil toxicity tests using soybean (Glycine max L.), the W3 and Lubrax dielectric fluid were used. The biodegradability analysis was evaluated by the action of microorganisms that transformed the sample into CO2, being measured by titulometry. For the acute toxicity studies, two distinct experiments were performed, where the organisms were exposed to different concentrations of the W3 and Lubrax dielectric fluids and to the FSA of the fluids. The FSA of W3 and Lubrax used in the Danio rerio assay were subjected to gas chromatography analysis. The acute toxicity tests with Danio rerio and Artemia salina were carried out in order to know the approximate range of fluid toxicity, taking into account the lower dilution that caused lethality in 50% of organisms (LC50). The soil chemical attributes analyzed were: pH, P, K, Ca, Mg, CTC and V. The content of oils and greases of the dielectric fluids was quantified by the Soxhlet type extraction method. For the phytothecnical evaluations, emergence, plant height, stem diameter, root length, root dry matter, number of pods and grains, and the mass of one thousand grains were analyzed. Vegetable dielectric fluids are biodegradable over a period of 14 days, while mineral oil is difficult to biodegrade. In the acute toxicity study, W3 had a lower LC50 than Lubrax, causing higher mortality in the organisms. The LC50 for the Danio rerio was 2.46 gL-1 (Lubrax) and 0.318 gL-1 (W3). For Artemia salina the LC50 was 4.63 gL-1 (Lubrax) and 0.641 gL-1 (W3). In relation to the FSA tests, the Lubrax one caused a greater toxic effect on the organisms, while the W3 had no toxic effect on 50% of organisms. The LC50 values for Lubrax were 4.89% for the Danio rerio and 7.67% for Artemia salina. Chromatographic analysis of FSA of the fluids was not conclusive, it only suggests that the toxicity may be related to the solubility of all the substances present in Lubrax and not only to the solubility of n-alkanes. The chemical attributes of the soil did not change significantly, only the carbon presented increasing variation in relation to the concentrations of the fluids. There was a reduction of the TOG during the agricultural years and the soils in the presence of W3 presented greater degradation than those with Lubrax. The increase in the concentration of the dielectric fluids caused a reduction in the phytotechnical characteristics of the soybean. Plants from soil contaminated with W3 showed better development compared to plants that were in soil contaminated with Lubrax. / As concessionárias de energia, constantemente, contaminam o meio ambiente com fluidos dielétricos, devido a falhas e vazamentos de transformadores de potência. Desta forma, estes fluidos devem ser estudados, pois podem pode implicar na vulnerabilidade da fauna e da flora. Neste sentido, este trabalho teve como objetivo investigar os efeitos deletérios do fluido dielétrico vegetal e mineral, através de ensaios de biodegradabilidade, toxicidade aguda, ensaios dos atributos químicos e degradação (óleos e graxas) do solo e das avalições das características fitotécnicas da soja. Nos ensaios da biodegradabilidade imediata foram estudados os fluidos dielétricos vegetais de crambe, W3, W6 e W9 e um à base de óleo mineral (Lubrax). Para os ensaios de toxicidade aguda com Danio rerio e Artemia salina e para os ensaios de toxicidade em solo utilizando a soja (Glycine max L.), foram usados o fluido dielétrico W3 e o Lubrax. A análise da biodegradabilidade foi avaliada pela ação de microrganismos que transformaram a amostra em CO2, sendo medido por titulometria. Para os estudos da toxicidade aguda foram realizados dois experimentos distintos, onde os organismos foram expostos às diferentes concentrações de fluido dielétrico W3 e Lubrax e onde foram expostos à FSA dos fluidos. A FSA do W3 e Lubrax utilizado no ensaio com o Danio rerio foram submetida a análise de cromatografia gasosa. Os ensaios de toxicidade aguda com o Danio rerio e a Artemia salina foram realizados com o intuito de se conhecer a faixa aproximada de toxicidade dos fluidos, levando em consideração a menor diluição que causou letalidade em 50% dos organismos (CL50). As análises dos atributos químicos do solo foram: pH, P, K, Ca, Mg, CTC e V. O teor de óleos e graxas dos fluidos dielétricos foi quantificado pelo método de extração em aparelho tipo Soxhlet. Para as avaliações fitotécnicas da soja analisou-se a emergência, altura de planta, diâmetro do caule, comprimento radicular, matéria seca radicular, número de vagens e de grãos e a massa de mil grãos. Os fluidos dielétricos vegetais são biodegradáveis num período de 14 dias, enquanto o óleo mineral é difícil de ser biodegradado. No estudo da toxicidade aguda o W3 apresentou uma CL50 menor do que o Lubrax, causando maior mortalidade nos organismos. A CL50 para o Danio rerio foi de 2,46 gL-1 (Lubrax) e de 0,318 gL-1 (W3). Para a Artemia salina a CL50 foi de 4,63 gL-1 (Lubrax) e 0,641 gL-1 (W3). Em relação aos ensaios com a FSA, o Lubrax causou maior efeito tóxico aos organismos. O W3 não apresentou efeito tóxico a 50% dos organismos. Os valores da CL50 para o Lubrax foi de 4,89% para o Danio rerio e 7,67% Artemia salina. A análise cromatográfica da FSA dos fluidos não foi conclusiva, apenas sugere que a toxicidade pode estar relacionada com a solubilidade de todas as substâncias presentes no Lubrax e não apenas com a solubilidade dos n-alcanos. Os atributos químicos do solo não sofreram alterações significativas, apenas o carbono apresentou variação crescente em relação às concentrações dos fluidos. Houve redução do TOG durante os anos agrícolas e os solos em presença do W3 apresentaram maior degradação do que os em solos com Lubrax. O aumento da concentração dos fluidos dielétricos ocasionou redução nas características fitotécnicas da soja. As plantas em solo contaminadas com W3 apresentaram melhor desenvolvimento em relação às plantas que estavam no solo contaminado com Lubrax.

Les céréales et les produits issus de leur transformation sont susceptibles d’être contaminés par des espèces fongiques capables de produire des mycotoxines. L’Homme est ainsi exposé tout au long de sa vie à travers son alimentation à ces contaminants naturels, généralement à de faibles doses et en mélange. Cependant, l’incidence de la présence simultanée de ces toxines sur notre santé, à court terme comme à plus long terme, ainsi que les mécanismes responsables de leur toxicité sont encore peu ou mal caractérisés. L’utilisation de modèles cellulaires humains pertinents et adaptés est particulièrement importante pour de telles études. L’épithélium intestinal et le système immunitaire, qui constituent la première barrière de défense de l’hôte suite à l’ingestion de contaminants alimentaires, ainsi que le foie, de par son rôle majeur dans la biotransformation des xénobiotiques, représentent des modèles d’étude pertinents en toxicologie. Dans le cadre de cette étude, des modèles cellulaires humains d’origine intestinale (Caco-2), immunitaire (THP-1) et hépatique (HepaRG) ont été employés pour évaluer le risque associé à la co-exposition aux mycotoxines de Fusarium (appelées fusariotoxines) qui sont parmi les plus problématiques dans nos régions. Différents types d’interactions, tels que de l’antagonisme et du synergisme, ont pu être observés sur la viabilité cellulaire en fonction de la nature du mélange, des doses testées, de la lignée cellulaire étudiée et du modèle mathématique utilisé pour prédire les effets combinés. Des interactions ont également été observées à l’échelle moléculaire, les effets des mélanges étant très différents de ceux induits par les toxines individuellement sur le protéome des cellules. D’autres résultats obtenus interrogent sur la façon dont les mycotoxines déclenchent réellement la réponse cellulaire. De plus, les interactions entre cellules cocultivées semblent capables de modifier la réponse cellulaire suite à l’exposition à ces toxines. Ces résultats soulignent l’importance de développer des modèles in vitro de plus en plus sophistiqués et s’approchant des conditions in vivo pour permettre une meilleure caractérisation du risque « mycotoxine ». / Cereals and cereal-based products are susceptible to be contaminated by mycotoxin-producing fungi.Thus, through their diet, humans are exposed throughout their life to these natural food contaminants, mostly at low doses and in mixture. However, the health impact of the simultaneous exposure to these toxins, in acute and chronic conditions, as well as the mechanism related to their toxicity, are still poorly characterized. The use of relevant and suitable human cell models is therefore of particular importance for such studies. The intestinal epithelium and immune system, which constitute the first host defense barrier following the food contaminant uptake, as well as the liver, due to its major function in xenobiotic biotransformation, are relevant for toxicity studies. In the framework of study, the intestinal (Caco-2), immune (THP-1) and hepatic (HepaRG) human cell models were used for risk assessment associated with co-exposure to Fusarium mycotoxins (called fusariotoxins) which are the most problematic in our regions. Different type of interactions, such as antagonism and synergism, were observed on cell viability depending on the nature of the mixture, tested concentration, studied cell line and used mathematical model to predict the combined effects. Interactions were also highlighted at the molecular level, the effects of mixtures being very different from those induced by the toxins alone on the cell proteome. Other results raised the question about how mycotoxins actually trigger the cellular response. In addition, cell-cell interactions in co-cultured systems appeared to modify the cellular response following exposures to these toxins. Overall, the obtained results highlighted the relevance of developing in vitro models increasingly sophisticated and closer to in vivo conditions to allow for a better characterization of the "mycotoxin" risk.