Polycyclic aromatic hydrocarbons (PAHs) are a well studied and diverse class of environmental toxicants. PAHs act via the aryl hydrocarbon receptor (AhR), and studies have suggested that PAHs may elicit neurological and estrogenic effects. Doses of PAHs between 50 to 150 ppm may elicit neurotoxicity in rodent models. The present study investigated the effects of naphthalene on in vivo steroidogenesis in Swiss Webster male mice, and in vitro neural function of Balb-C/ICR mice frontal cortex neurons. These data suggest that naphthalene may not elicit steroidogenic effects at concentrations ranging from 0.2 to 25 mg/kg/day, following a 7 day subcutaneous dosing regime. In addition, naphthalene may cause functional toxicity of frontal cortex neurons at concentrations of 32 to 160 ppm naphthalene.

Wood is a natural raw material, and would hardly be considered a risk to the environment. However, the handling of wood materials on an industrial scale has been shown to have a negative impact on water bodies that run-off from industrial sites that process wood-based materials. Most investigations related to water pollution from wood-based industries have focused on large industrial sites such as pulp and paper mills. The goal of the present thesisis to understand better such environmental problems and treatment solutions that occur at most wood handling sites. Where there are large outdoor storage areas for logs and sawdust that are exposed to rainfall or irrigation, such as the wooden-floor and bio-energy sectors. Leachate generated by the contact of water with wood in storage areas contains a large amount of organic matter that is potentially hazardous to water bodies that receive run-off from the site. It has been found that different wood species yield different leachate compositions, with leachate from oak having the highest pollutants content, followed by leachate from pine. This investigation shows that oak has the potential to leach about 10 times the amount of polyphenols compared with other investigated species (i.e., pine, beech and maple). Furthermore, oak leachates have the lowest ratio of biological oxygen demand at 7 days tochemical oxygen demand (0.12), which suggests a potential problem with the biological degradation of this leachate. It has also been shown that leachate from wood are potentially toxic to aquatic organisms. Treatability studies with the aim of reducing the environmental impact of wood leachate were conducted on a pilot scale as part of the scope of this thesis. The results showed, among other options, the possibility of using constructed wetlands to treat leachate. It was found that plants and aeration can affect the performance of a wetland. However, the most important factor is the time water spends in the wetland. Filter material that could be used to absorb leachate was also studied. A filter consisting of a mixture of peat and ash (from incinerated organic matter), was used to absorb a specific chemical group (polyphenols) in the leachate. It was also shown that polyphenols are vulnerable to ozone, representing a third viable treatment process. / Trä är ett naturligt råmaterial som knappast anses vara en risk för miljön. Däremot har hanteringen av trämaterial i industriell skala visat sig ha negativ inverkan på vattendrag. De flesta utredningar avseende vattenföroreningar inom träbaserade industrier har fokuserat på stora industrier med stor vattenförbrukning så som massa- och pappersbruk. Lakvatten som alstras vid kontakten mellan vatten och trä innehåller höga halter av organiska ämnen som är potentiellt farliga för vattendrag. Målet med denna avhandling är att få kunskap om ovanstående miljöproblem och möjlig behandlingar av dessa. Förorenat lakvatten skapas av industrier, där stora mängder timmer och sågspån är placerade utomhus och utsätts för regn och bevattning, såsom inom trägolv och bioenergisektorn. Man har funnit att lakning från olika träslag ger olika sammansättningar på lakvattnet, där lakvatten från ek har den högsta halten av föroreningar följt av furu. Denna undersökning visar att ek har potential att laka ut tio gånger så mycket polyfenoler jämfört med andra undersökta arter (tall, bok och lönn). Dessutom har lakvatten från ek den lägsta andelen av biologisk syreförbrukning efter 7dagar per kemisk syreförbrukning (0,12), vilket tyder på ett potentiellt problem med den biologiska nedbrytningen av detta lakvatten. Man har även påvisat att lakvattnet från trä är potentiellt giftigt för akvatiska organismer. Studier för att försöka minska miljöpåverkan av lakvatten från denna trädsort gjordes i pilotskala inom ramen för denna avhandling. Dessa studier visade bland annat på möjligheterna att använda sig av våtmarker som reningsmetod, där växter och luftning påverkar hur bra en våtmark fungerar. Men den viktigaste faktorn var den ökade uppehållstiden som vattnet får i våtmarken. Utöver studier av våtmarker har också ett filtermaterial studerats, filtret bestod av en blandning av torv och aska, som användes för att absorbera en specifik kemisk grupp i lakvattnet (polyfenoler). I en tredje typ av behandlingsprocess visade det sig också att polyfenoler effektivt kan brytas ned av ozon.

Biocide-based antifouling (AF) paints are the most common method for preventing biofouling, i.e. the growth of algae, barnacles and other organisms on boat hulls. AF paints for leisure boats are predominantly based on copper (Cu) as the main biocide, with zinc (Zn) present as a pigment and stabilizer. Both metals are released from the paint matrix into the water column, leading to contamination of marinas which typically have only limited water exchange. Thus, the aim of this PhD thesis was to describe the use of AF paints in different regions in Sweden, as well as the associated environmental consequences with regard to contamination of the environment and toxicity to non-target aquatic snails. Using a recently developed X-ray fluorescence application, high levels of Cu were detected on boats moored in freshwaters, despite a more than 20-year-old ban, as well as high levels of tin (Sn) on 10 % of the boats, indicating the presence of (old) tributyltin paints (TBT), which might pose an environmental risk and a health hazard for people performing the paint scraping (paper 1). In addition, very high levels of Cu and Zn were measured in the biofouling material collected from the boat hulls, and this is problematic because the biofouling is commonly disposed of on the soil in boatyards at the end of each season. No difference was found in the amount of biofouling on boats coated with Cu or biocide-free paints, which implies that Cu might be currently overused in areas of low salinity and low barnacle density (paper 2). This work also introduces the use of a new species for ecotoxicological field experiments, the snail Theodoxus fluviatilis. Chronic field experiments (paper 3) revealed 6-fold increases in snail mortality, negative growth and up to 67-fold decreased reproduction in marinas, compared to areas not impacted by boating (‘reference areas’). Moreover, a higher prevalence of snails with histopathological alterations (e.g. necrosis of gills, gonads, midgut gland and parasite infestation, among others) was observed in the marinas, compared to the reference areas (paper 4). Statistical modelling indicated that the majority of the toxic effects were best predicted by the metals, most likely originating from AF paints. The results presented in this thesis depict some important aspects of AF paint use in brackish water and highlight the necessity of implementing a suitable management practice for the heavily contaminated biofouling waste in order to minimize the risk to soils. In addition, the evidence of toxicity to snails in marinas can be used as a basis to increase the public understanding of the impact of recreational boating and encourage people to choose less toxic alternatives to AF paints. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

Nanoobjekte werden als eines der meist untersuchten Forschungsgebiete unserer Zeit immer beliebter in der Industrie, da durch Variation ihrer Strukturen besondere Eigenschaften entlockt werden können, die bei makrokristallinen Kompositionen nicht auftreten. Doch mit Zunahme der Anwendungsbereiche steigt wiederum die Wahrscheinlichkeit einer hohen Exposition, was die toxikologischen Untersuchungen der letzten Jahre bedingte. Allerdings wurden dabei weniger die kausalen Zusammenhänge eruiert. In dieser Arbeit zeigt der Autor die Beziehungen zwischen ZnO-Toxizität und intrazellulärer Zn2+-Konzentrationen auf. Zu diesem Zweck erfolgten Zytotoxizitätsuntersuchungen mittels MTT-Test von ZnO-Nanopartikeln und ZnCl2. Dadurch konnten die toxischen Eigenschaften dieser Agenzien belegt werden. Sowohl Nanopartikel als auch Zn2+ weißen in äquivalenter Gesamtmasse dieselben Toxizitätswerte auf. Nachfolgend wurde die Toxizität I) der Partikel durch Chelatierung der Ionen und II) der freigesetzten Zn2+ durch Abzentrifugieren der Partikel untersucht. Hierbei zeigte sich eine deutlich niedrigere Toxizität der Partikel in Abwesenheit von Zn2+. Hingegen verursachten die partikelfreien Proben allein durch die freigesetzten Zn2+ durchaus vergleichbare Effekte wie die ZnO-Dispersion. Erwähnenswert ist, dass generell eine geringere Toxizität durch FKS-Zugabe vorhanden war. Im Weiteren wurde die intrazelluläre Zn2+-Konzentration in Abhängigkeit der Zinkexposition untersucht. Anhand der Markierung mit dem zinkspezifischen Fluorophor FluoZin-3 erfolgte die quantitative Zn2+-Bestimmung mittels Durchflusszytometrie. Dabei ergab sich ein signifikanter Anstieg der intrazellulären Zn2+-Konzentration, der eine einschneidende Störung der Zinkhomöostase darstellt. Bemerkenswert ist der Anstieg in vitalen Zellen auf ein Vielfaches der Ausgangkonzentration, wobei das Überschreiten von etwa 10 nM zum Übergang in die Nekrose führte. Unabhängig von äußeren Faktoren lagen bei gleichen Toxizitätswerten vergleichbare intrazelluläre Zn2+-Konzentrationen vor. Offenbar gibt es einen direkten Zusammenhang zwischen intrazellulären Zn2+ und der Toxizität. Dieser Sachverhalt kann zur Risikobewertung der Nanopartikel herangezogen werden.

Environmental contamination with heavy metals, especially of soils, has been a continuousproblem worldwide since the beginning of the industrial revolution. Heavy metal emissionshave increased continuously since 1900 and the metals accumulate in the environment. Pulpand paper mill factories, and factories which produce sulphuric acid emit heavy metals,among others lead (Pb), copper (Cu) and zinc (Zn). Results from previous studies showedthat the soils near factories had higher concentrations of these pollutants than the controlplace. In this study I want to determine the effects of industrial heavy metal emissions of onehistoric and one present industry on nearby soil heavy metal concentrations.Samples were taken near one historically heavily contaminated site, the old sulphite factoryin Rydöbruk (1897-1944) and near the present Stora Enso paper mill in Hyltebruk. As acontrol site, I compared these with Rocknen nature reserve area.At each site I took 6 soil samples, representing the top 15-20 cm of soil and organic material.Samples were analysed with an Atomic Absorption Spectrometer and the concentrations oflead, copper and zinc were determined per ashed dry material.I analyzed the samples at the laboratory using the guideline from the Swedish StandardInstitute for water analysis.The concentrations of the soil samples showed no significant difference between the naturereserve area and the industrial sites (One-way ANOVA). This was due to very variableorganic content within and between the sites.Organic content of the samples has a significantly effect on the metal concentrations for Pband Cu (Linear Regression test). In conclusion, metals can accumulate in the vegetation, andin case of Pb and Cu there is a correlation between their concentration and the amount oforganic matter. Therefore in future studies it is best if soil with very high organic content orvegetation is used to determine if forest soil near industries are affected by past or presentindustrial emissions of heavy metals.

L’objectif de ce travail de thèse est de développer de nouveaux agents tensioactifs, capables de s’auto-assembler sous forme de micelles permettant de solubiliser les principes actifs insolubles, en vue de leur administration par voie intraveineuse. Cette étude a permis la synthèse, la caractérisation physico-chimique ainsi que l’évaluation toxicologique in vitro et in vivo de nouveaux agents tensioactifs d’origine naturelle. Au cours de cette étude, différentes familles de tensioactifs ont été évaluées. Ces nouveaux agents tensioactifs sont composés d’une partie hydrophobe de type cholestérol, sels biliaires ou lipides, associée via une fonction amide à une partie hydrophile dérivée d’acides aminés tels que la lysine, la glutamine ou l’acide glutamique.Ces travaux expérimentaux ont permis d’étudier l’influence de la flexibilité de la partie hydrophobe sur la capacité de solubilisation des tensioactifs. Cette étude a montré que l’efficacité de solubilisation est reliée à la flexibilité de la partie hydrophobe. L’utilisation d’agents tensioactifs composés d’une chaîne lipidique saturée flexible a permis de solubiliser efficacement le principe actif insoluble avec un taux de charge de 46 % (m/m). Les tensioactifs composés de lipides saturés sont donc plus efficaces en termes de solubilisation que les dérivés de stéroïdes ou de lipides polyinsaturés, moins flexibles. Les études de toxicité ont mis en évidence la relation ente la structure chimique des tensioactifs et leur toxicité, en particulier vis-à-vis des membranes cellulaires. L’introduction de doubles liaisons en configuration cis dans la partie lipidique des tensioactifs permet de diminuer leur interaction avec les membranes cellulaires et donc leur toxicité mais diminue également leur capacité de solubilisation. Le développement de nouveaux agents tensioactifs nécessite donc de trouver un compromis entre la capacité de solubilisation et la toxicité des tensioactifs. / The aim of this thesis was to develop novel surfactants, able to self-assemble into micelles and to solubilize insoluble drugs intented for intravenous injection. Natural-based surfactants were synthesized and their physico-chemical properties were evaluated. In addition, their in vitro and in vivo toxicity were evaluated. Their drug solubilization abitity was also investigated. Three surfactant classes were evaluated. They were composed of a hydrophobic moiety, such as cholesterol, bile salts or lipids, bonded to a hydrophilic moiety, deriving from amino acids, such as lysine, glutamine or glutamic acid, via an amide bond.The influence of surfactant hydrophobic moiety flexibility on drug solubilization ability was evaluated. This study evidenced that solubilization efficiency is related to the surfactant hydrophobic moiety flexibility. The use of surfactants with flexible and saturated lipidic moieties increased drug water solubility with a drug loading of 46 % (w/w). Saturated lipid-based surfactants exhibited a better solubilization efficiency, in comparison with steroid-based surfactants or poly-unsaturated-based surfactants. Toxicity studies evidenced the relation between surfactant chemical structure and their toxicity, in particular with cell membranes. The introduction of double bond in cis configuration in surfactant lipidic moiety decreased their interaction with cell membranes and thus their toxicity. In addition, this chemical modification also decreased their solubilization ability. To develop novel surfactants, it is thus necessary to take into account drug solubilization ability and toxicity of surfactants.

En cas de contamination cutanée radiologique par des composés d’uranium, les seuls traitements actuellement employés consistent en un rinçage de la zone contaminée par de l’eau et des détergents, ou par une solution de sel calcique de l’acide diéthylène-triamine-pentaacétique (Ca-DTPA). Ces derniers ne sont cependant pas efficaces vis-à-vis de l'uranium. De plus, en l'absence de traitement d'urgence, le passage transcutané de ce radionucléide est rapide, et induit une exposition interne après sa distribution dans l’organisme par le biais de la circulation sanguine. Une partie de l'uranium ainsi biodisponible est alors stockée dans les organes cibles que sont principalement les reins et le squelette, où ses effets toxiques se manifestent. C'est pourquoi une formulation topique consistant en une nanoémulsion huile dans eau, incorporant des molécules de calixarène tricarboxylique en tant qu'agent chélatant spécifique de l'uranium, a été initialement développée. Les travaux menés dans le cadre de cette thèse visent à évaluer l'efficacité de décontamination ex vivo et in vivo de ce nouveau traitement d'urgence à la fois sur peaux intactes et sur peaux lésées superficiellement. Pour cela, le modèle d'excoriation a été utilisé. Des modèles de lésions reproductibles ont également été mis en place afin de mimer des incisions par micro-piqûres et microcoupures. Ces études démontrent que la nanoémulsion de calixarène pourrait constituer un traitement de décontamination efficace, moins agressif que l’emploi de l’eau savonneuse actuellement employée. Sa potentielle toxicité cutanée a également été évaluée in vitro par l'utilisation d'épiderme humain reconstitué, combinée à trois différents tests de toxicité (MTT, LDH et IL-1-α). Dans le cadre de ces études, il a ainsi été démontré que la nanoémulsion de calixarène n’induit pas de toxicité cutanée, même après un temps de contact prolongé jusqu'à 24 h. / In case of radiological skin contamination by uranium compounds, the only treatments currently available consist in rinsing the contaminated skin area with water and detergent, or with a calcium salt of diethylene triamine pentaacetic acid (Ca-DTPA) solution. However, these procedures are not specific and no efficient treatment for cutaneous contamination due to uranium exists. In the absence of such treatments, uranium diffusion through the skin is fast, inducing an internal exposure after its distribution inside the body through the bloodstream. One part of the bioavalaible uranium is uptaken in target organs which are the kidneys and the skeleton, where its toxic effects occur. Therefore a topical formulation consisting of an oil-in-water nanoemulsion incorporating a tricarboxylic calixarene molecule, as a specific chelating agent for uranium, was previously developed. The work achieved in this thesis aimed at evaluating the ex vivo and in vivo decontamination efficiency of this new emergency treatment on intact and superficially wounded skin. For this purpose, skin excoriation model was used. Reproducible models of superficial wounds consisting of micro-cuts and micro-punctures were also developed in order to evaluate the efficiency of the nanoemulsion on physical wounds such as incisions. These studies showed that the calixarene nanoemulsion could be an efficient decontaminant treatment, less aggressive than using the current treatment: soaped water. Its potential cutaneous toxicity was evaluated on in vitro reconstructed human epidermis using three different toxicity tests (MTT, LDH and IL-1-α). These studies demonstrated that the calixarene nanoemulsion did not induce skin toxicity even after 24 h of exposure time.

Du fait de leurs exceptionnelles propriétés, un très vaste champ d'applications s'ouvre aux nanotubes de carbone. La connaissance de leur toxicité est un enjeu primordial afin de connaître les risques et les dangers que ces objets représentent.Le travail présenté dans cette thèse vise à la synthèse de dérivés ayant pour but de favoriser les interactions entre les nanotubes et le milieu vivant.La synthèse d'une série de dérivés du cholestérol utilisables pour la fonctionnalisation des nanotubes de carbone a été mise au point. L'utilisation de tels dérivés a pour but de favoriser les interactions entre les objets greffés et les membranes cellulaires.Par ailleurs, de nombreux intermédiaires de synthèse présentent des propriétés mésomorphes. Celles-ci ont été étudiées au moyen de différentes méthodes telles que la microscopie optique, la calorimétrie différentielle à balayage et la diffusion des rayons X.Des nanotubes HiPco ont pu être purifiés et fonctionnalisés. L'analyse de leur cytotoxicité a été abordée, celle-ci a permis de mettre en avant une diminution de la toxicité des nanotubes greffés comparée à celles de nanotubes purifiés. / Synthesis and study of mesomorphic properties of grafts for carbon nanotubes functionalizationIn order to study the toxicity of carbon nanotubes, cholesterol based derivatives were synthesized. Due to their exceptional properties, a wide field of applications is opened for carbon nanotubes. Regarding this field, knowing their toxicity becomes a key issue.The work presented here aims towards the synthesis of chemical derivatives designed to increase interactions between carbon nanotubes and a biological environment. The synthesis of a series of cholesterol derivatives aimed for the functionalization of carbon nanotubes has been developed. Such derivatives are intended to interact with cell membranes.Moreover, many synthetic intermediates have mesomorphic properties. These properties have been studied using different methods such as polarized optical microscopy (POM), differential scanning calorimetry (DSC) and X-ray scattering (MWAXS).HiPco nanotubes have been purified, functionalized and characterized with techniques such as Raman spectroscopy and X-ray diffraction (XRD).Finally, a study of carbon nanotubes toxicity is presented.

A cafeína está presente no cotidiano humano desde o tradicional café até como constituinte de medicamentos, estimulantes, chás, chocolate entre outros produtos alimentícios. Essa substância é considerada um contaminante orgânico emergente provindo de águas residuárias não tratadas. Sua presença nos corpos hídricos vem sendo documentada em baixas concentrações, desde &eta;g.L-1 até &#181;g.L-1 e os efeitos dessas concentrações nos organismos aquáticos ainda não foram efetivamente investigados. Com o objetivo de avaliar os efeitos tóxicos da cafeína em concentrações comumentemente encontradas em corpos hídricos, foram realizados testes de ecotoxicidade aguda e crônica com os organismos-teste Chironomus sancticaroli e Daphnia magna e intergeracional com C. sancticaroli, com enfoque em respostas biológicas de mortalidade, imobilidade, crescimento, desenvolvimento e reprodução. Como resultado, a cafeína não apresentou toxicidade aguda no teste de curta duração realizado para D. magna e C. sancticaroli. Foi observado efeito de toxicidade crônica da cafeína, havendo interferência no desenvolvimento das larvas de Chironomus principalmente na concentração de 200 &#181;g.L-1 e no crescimento e reprodução de D. magna, na qual foi observada indução na produção de neonatos e desaceleração para o desenvolvimento do organismo (retardo no processo de ecdise). No teste intergeracional, foram observadas mudanças nos padrões de desenvolvimento larval. Os resultados demonstram que a cafeína, em concentrações ambientalmente detectadas, pode causar pequenas alterações no ciclo de vida dos organismos, como por exemplo, alterações no tamanho das asas das fêmeas e no comprimento do corpo das larvas de C. sancticaroli. Recomendam-se o uso de técnicas biomoleculares para avaliar as respostas metabólicas dos organismos quando exposto à cafeína em baixas concentrações. / Caffeine is present in human daily life either as traditional coffee or constituent of medicines, stimulants, teas, chocolate, among other products. This substance is an emerging organic contaminant from untreated wastewater. Its presence in aquatic systems has been documented at low concentrations, from &eta;g.L-1 to &#181;g.L-1 and the effects of these concentrations on aquatic organisms have not yet been effectively investigated. In order to evaluate the toxic effects of caffeine, at concentrations usually found in aquatic systems, acute and chronic ecotoxicological tests were performed with Chironomus sancticaroli and Daphnia magna and, an intergenerational with C. sancticaroli, focusing on biological responses of mortality, immobility, growth, development and reproduction. As a result, caffeine did not present acute toxicity in the shor-term test performed for D. magna and C. sancticaroli. Chronic toxicity of caffeine was observed, with interference in the Chironomus larvae development, mainly in the concentration of 200 &#181;g.L-1, and in the growth and reproduction of D. magna, in which it was observed presence of induction in the production of neonates and deceleration to the development of the organism (delay in the process of ecdysis). In intergeneration test, changes in the larval developmental patterns were observed. In intergenerational testing, changes in larval developmental patterns were observed. The results demonstrate that caffeine, in concentrations detected environmentally, can cause small influences in the organism\'s life cycle of the, for example, changes in the size of the wings of the females and in the length of the body of the larvae of C. sancticaroli. The use of biomolecular techniques to evaluate the metabolic responses of organisms when exposed to caffeine at low concentrations is recommended.

Orientador: Daniela Carvalho dos Santos / Resumo: O bicho-da-seda, Bombyx mori (Lepidoptera: Bombycidae), é o inseto de maior importância econômica na produção de seda. A lagarta se alimenta de folhas de amoreira e é altamente sensível a agrotóxicos, assim o uso destes em culturas agrícolas circunvizinhas às plantações de amoreira pode afetar o desenvolvimento de B. mori, acarretando em desequilíbrio nas suas funções metabólicas e, consequentemente, comprometendo a produção de casulos. Entre estes agrotóxicos, destaca-se o Novaluron, inseticida inibidor da síntese de quitina nos insetos e empregado no controle de insetos pragas de culturas agrícolas próximas as plantações de amoreira. Assim, investigamos os efeitos tóxicos de Novaluron no desenvolvimento de B. mori. Lagartas de B. mori, foram separadas em dois grupos experimentais: grupo controle (GC) e grupo tratamento (GT: tratado com 0, 15 mL/L de Novaluron). Após ecdise do 2° para o 3° instar, lagartas do GT foram alimentadas por 24 horas com folhas de amoreira tratadas com o inseticida. Paralelamente foi realizada uma nova exposição, porém em lagartas que realizavam a ecdise do 4° para o 5° instar. Lagartas, pupas e adultos de B. mori foram anestesiadas e segmentos do intestino médio, glândula da seda e órgãos reprodutores retirados e processados convencionalmente para técnicas de microscopias de luz, eletrônica e imunohistoquímica. Além disso, os efeitos no desenvolvimento, reprodução e qualidade do casulo também foram avaliados. O Novaluron provocou efeitos citotóxico... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The silkworm, Bombyx mori (Lepidoptera: Bombycidae is the insect of major economic importance in the production of silk. The larvae feeds on mulberry leaves and is highly sensitive to agrochemicals, thus the use of these in agricultural crops surrounding the mulberry plantations can affect the development of B. mori, causing an imbalance in its metabolic functions and, consequently, compromising the production of cocoons. Among these agrochemicals, stands out the Novaluron, an insecticide inhibitor of the synthesis of chitin in insects and used in the control of insect pests of crops near mulberry plantations. Thus, we investigated the lethal and sublethal effects of Novaluron on the development of B. mori. Larvae were selected into two experimental groups: control group (CG) and treatment group (TG: treated with 0, 15 mL/L Novaluron). After ecdysis from the 2nd to the 3rd instar, the TG larvae were fed for 24 hours with mulberry leaves treated with the insecticide. In parallel, a new exposition was carried out, however in larvae that carry out the ecdysis from the 4th to the 5th instar. B. mori larvae, pupae and adults were anesthetized and segments of the midgut, silk gland and reproductive organs were removed and processed conventionally for light microscopy, electron microscopy and immunohistochemistry. In addition, the effects on the development, reproduction and quality of the cocoon were also evaluated. Novaluron caused cytotoxic effects on the midgut and the silk glan... (Complete abstract click electronic access below) / Doutor