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Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2008. / Härtill 4 uppsatser.

Ένα από τα μεγαλύτερα περιβαλλοντικά προβλήματα που αντιμετωπίζει όχι μόνο ο Νομός Αχαΐας, αλλά και πολλές άλλες περιοχές της χώρας μας, είναι η υποβάθμιση του περιβάλλοντος από μια σειρά αποβλήτων αγροτοβιομηχανιών που υπάρχουν στην ελληνική ύπαιθρο. Μεταξύ των αγροτοβιομηχανιών σημαντική θέση κατέχουν οι μονάδες επεξεργασίας γάλακτος και παραγωγής τυριού. Παρά το ότι η παραγωγή γάλακτος και γαλακτοκομικών προϊόντων είναι σχετικά περιορισμένη στο Νομό Αχαΐας, ωστόσο η διάσπαρτη κατανομή τους σε συνδυασμό με τις κρατούσες συνθήκες λειτουργίας τους συμβάλλει σημαντικά στη ρύπανση του περιβάλλοντος της περιοχής. Είναι γεγονός ότι οι περισσότερες αγροτοβιομηχανίες, όπως τα τυροκομεία, λειτουργούν σε περιοδική βάση αφού τα προϊόντα τους είναι εποχικά, τα εργοστάσια είναι διασκορπισμένα σε μεγάλες αποστάσεις και οι μονάδες είναι σχετικά μικρές. Τα απόβλητα που παράγονται από τις τυροκομικές μονάδες έχουν υψηλό οργανικό φορτίο και από προηγούμενη έρευνα έχει προσδιοριστεί ότι είναι τοξικά και αποτελούν αιτία υποβάθμισης των υδάτινων οικοσυστημάτων. Η παρούσα μελέτη έχει ως βασικό σκοπό την εκτίμηση της τοξικότητας των αποβλήτων που προέρχονται από τυροκομεία μετά από την επεξεργασία τους για παραγωγή βιαερίου (υδρογόνου και μεθανίου) σε αντιδραστήρες αναερόβιας χώνευσης (Η2-CSTR και CH4-CSTR αντίστοιχα), με σκοπό την συνολική εκτίμηση των επιπτώσεών τους στο υδάτινο οικοσύστημα. Αρχικά εκτιμήθηκε ο οικολογικός κίνδυνος από την απόρριψη των αποβλήτων μιας τυροκομικής μονάδας στο ποτάμι του Βουραϊκού. Τα δεδομένα που συγκεντρώθηκαν δίνουν ετήσια πρόβλεψη για κρίσιμα επίπεδα οικολογικού κινδύνου σε εποχές όπως είναι το καλοκαίρι όπου η ροή νερού στο ποτάμι είναι μικρή, και για μικρότερο, αλλά και πάλι αξιοσημείωτο επίπεδο κινδύνου κατά το φθινόπωρο. Οι βροχοπτώσεις είναι λογικό να δημιουργούν μεγαλύτερη αραίωση του αποβλήτου στο νερό γεγονός που προκαλέι μείωση των επιπέδων κινδύνου. Η συνδυασμένη ανάλυση των δεδομένων απέδειξε ότι εξαιρετικά μικρή συγκέντρωση του αποβλήτου, μικρότερη του 0,064%, είναι προϋπόθεση για να αποφευχθεί ο οικολογικός κίνδυνος για την υδρόβια πανίδα. Όμως, η παρούσα οικολογική κατάσταση του οικοσυστήματος απέχει πολύ από το να χαρακτηριστεί ως βέλτιστη, μιας και η απόρριψη ανεπεξέργαστων αποβλήτων στο νερό προκαλεί συγκεντρώσεις 5 φορές μεγαλύτερες από το ανωτέρω όριο, πλησιάζοντας το 0,32% κατά τη διάρκεια του καλοκαιριού. Ο έλεγχος τοξικότητας επιτεύχθηκε με τη χρήση βιοδεικτών από δύο τροφικά επίπεδα (ασπόνδυλα και ψάρια του γλυκού νερού). Συγκεκριμένα, στην πρώτη περίπτωση χρησιμοποιήθηκαν δύο μακροασπόνδυλα (Daphnia magna και Thamnocephalus platyurus) με τη μορφή των μικροβιοτέστ Thamnotoxkit F και Daphtoxkit FTM magna, τα οποία επελέγησαν λόγω της αξιοπιστίας τους, της σχετικής ευκολίας τους στη χρήση, του χαμηλού κόστους και της προοπτικής τους να χρησιμοποιηθούν από μη εξειδικευμένο προσωπικό για την παρακολούθηση των επιπτώσεων των συγκεκριμένων αποβλήτων. Στη δεύτερη περίπτωση έγινε ο έλεγχος της τοξικότητας με έμβρυα zebrafish (Danio rerio) με βάση τα πρωτόκολλα των σχετικών ISO και της EPA. Λήφθηκαν συνολικά 109 δείγματα (4 διπλά δείγματα τυρόγαλου, 55 διπλά δείγματα από τον αντιδραστήρα παραγωγής υδρογόνου και 50 διπλά δείγματα από τον αντιδραστήρα παραγωγής μεθανίου). Στα τεστ τοξικότητας που εφαρμόστηκαν (Thamnotoxkit F, Daphtoxkit FTM magna και zebrafish), υπολογίσθηκαν τα L(Ε)C50 24h και 48h σύμφωνα με τα πρωτόκολλα εργασίας. Ευρέθη ότι το μεν Thamnocephalus platyurus είχε μέση τιμή LC50 ίση με 0,76 για τα δείγματα από τον αντιδραστήρα Η2-CSTR και 1,33 για τα δείγματα από τον αντιδραστήρα CH4-CSTR, οι αντίστοιχες τιμές για την Daphnia magna στις 48 ώρες ήταν 1,82 και 2,26 ενώ για το zebrafish 0,88 και 0,95 στο ίδιο διάστημα. Οι τιμές που προέκυψαν από τους τρεις ελέγχους κατατάσσουν τα απόβλητα από «πολύ τοξικά» έως «εξαιρετικά τοξικά». Από τη συσχέτιση των φυσικοχημικών παραμέτρων με τα L(Ε)C50 προκύπτει ότι για τα δείγματα του Η2-CSTR υπάρχει θετική συσχέτιση των αμμωνιακών, νιτρικών και νιτρωδών ιόντων με το Thamnocephalus platyurus (R= 0,368, R=0,442 και R=0,362 αντίστοιχα) και για τα δείγματα του CH4-CSTR συσχέτιση υπάρχει μόνο με τα ολικά διαλυμένα στερεά (R=0,860). Για το zebrafish, υπάρχει συσχέτιση με τα φωσφορικά (R= 0.542) και με τα αμμωνιακά ιόντα (R=0,562) για τα δείγματα του Η2-CSTR, ενώ για τα δείγματα του CH4-CSTR με τα φωσφορικά (R=0,963) και τα νιτρώδη ιόντα (R= 0,960). Η Daphnia magna δε δείχνει καμία σημαντική συσχέτιση, με τη μεγαλύτερη εξ αυτών να παρατηρείται με τα αμμωνιακά ιόντα (R= 0,316) μόνο για τα δείγματα του Η2-CSTR. Σύμφωνα με τα ανωτέρω αποτελέσματα τεκμηριώνεται ότι το Thamnocephalus platyurus και το zebrafish είναι οι πιο ευαίσθητοι και επομένως οι πλέον κατάλληλοι οργανισμοί για την εκτίμηση της τοξικότητας των συγκεκριμένων αποβλήτων. Η παρατήρηση σκελετικών δυσμορφιών έστω και σε μικρό ποσοστό δειγμάτων του zebrafish, οδήγησε στην ανίχνευση βαρέων μετάλλων σε όλα τα επεξεργασμένα δείγματα δεδομένου ότι και αυτά έχουν ενοχοποιηθεί για την πρόκληση αυτών. Συγκεκριμένα ανιχνεύθηκαν χρώμιο, μαγγάνιο, ψευδάργυρος και μόλυβδος, όμως ο ρόλος καθενός από αυτά ή και συνεργιστικά όλων αυτών στις παρατηρηθείσες δυσμορφίες δε μπορεί να διερευνηθεί πλήρως στα πλάισια αυτής της μελέτης και για τούτο θα απαιτηθεί περαιτέρω έρευνα. Συνοπτικά αποδεικνύεται ότι όλα τα επεξεργασμένα δείγματα και με τις δύο μεθόδους ήσαν τοξικά και όχι περιβαλλοντικά ασφαλή για άμεση διάθεση σε υδάτινο αποδέκτη χωρίς περαιτέρω επεξεργασία για την απομάκρυνση των υπόλοιπων επιβαρυντικών παραγόντων όπως ο φώσφορος και οι ενώσεις του αζώτου. Τέλος, θα πρέπει να σημειωθεί ότι η παρούσα μελέτη είναι η πρώτη μελέτη εκτίμησης της τοξικότητας των αποβλήτων των τυροκομικών μονάδων μετά από την επεξεργασία του για παραγωγή βιοαερίου που γίνεται στη χώρα μας, αλλά και γενικότερα δεν υπάρχει ανάλογη αναφορά στη διεθνή βιβλιογραφία. Δεδομένου ότι η προαναφερθείσα επεξεργασία αποτελεί μια καινοτομία συνδυασμένης μεθοδολογίας που αποβλέπει αφενός στην εξυγίασνη του αποβλήτου και αφετέρου στην παραγωγή ωφέλιμου παραπροϊόντος όπως είναι το βιοαέριο, τα αποτελέσματα αυτής της έρευνας θα μπορούσαν να αποτελέσουν ένα αξαιρετικά χρήσιμο εργαλείο, αφενός στους επιστήμονες που ασχολούνται με την επεξεργασία των αποβλήτων ώστε να αναζητήσουν τρόπους περαιτέρω αποφόρτισης αυτών από τους εναπομείναντες τοξικούς παράγοντες και αφετέρου στην πολιτεία για τη συστηματική παρακολούθηση και τον έλεγχο των συγκεκριμένων μονάδων στα πλαίσια εφαρμογής ορθής περιβαλλοντικής πολιτικής. / One of the major environmental hazard not only for the Achaia Prefecture, but also for many other regions of the Greek area has to deal with agro-industrial effluents which outfall to the countryside. Among the agro-industries, the units of milk treatment and cheese production are concerned as such of great environmental interest. Despite that the production of milk and dairy products is relatively limited in Achaia Prefecture, their scattered installation and their unlegal operation contribute considerably in the environmental pollution of the area. The most dairy units operate in periodical base, they are scattered in the countryside while they are relatively assessed as small units. Their effluents that have been considered as toxic. The basic aim of the present study is to estimate the toxicity of cheese whey effluents from dairy unit after their treatment for biogas production (hydrogen and methane) in anaerobic digestion reactors (H2-CSTR and CH4-CSTR respectively), aiming at the total estimation of their repercussions in the aquatic ecosystem. Initially, the ecological risk from the rejection of cheese-whey effluents in the river of Vouraikos has been estimated. The data drived to an annual forecast which gives critical levels of ecological risk during summertime, and remarkable level of risk during autumn. Integrated analysis proved that effluents concentration of the river smaller than 0,064% is prerequired in order to avoid the ecological risk of the aquatic fauna, while the present ecological situation of ecosystem is far from optimal, as the rejection of the untreated effluents into the water leads to concentrations 5 times higher than the above limit, approaching 0,32% during summertime. The toxicity estimation was achieved with the use of bioindicators from two trophic levels (freshwater invertebrates and fish): Daphnia magna and Thamnocephalus platyurus in the form of mikrobiotests Thamnotoxkit F and Daphtoxkit FTM magna, and the embryos of zebrafish (Danio rerio) according to the protocols of ISO and EPA. In total there have been taken 109 samples (4 duplicate samples of cheese whey, 55 duplicate samples from the reactor of hydrogen production and 50 duplicate samples from the reactor of methane production). In the toxicity tests applied (Thamnotoxkit F, Daphtoxkit FTM magna and zebrafish), L(E)C50 in 24h and 48h were calculated according to the tests protocols. It was found that mean LC50 values for the Thamnocephalus platyurus was 0.76 for the samples from H2-CSTR reactor and 1.33 for the samples from CH4-CSTR reactor. The corresponding values for Daphnia magna in the 48 hours was 1.82 and 2.26 while for the zebrafish 0.88 and 0.95 for the same period. The values resulted from the three tests classify the effluents from “very toxic” to “extremely toxic”. From the cross-correlation of physicochemical parameters with L(E)C50 results of Thamnocephalus platyurus, the samples of H2-CSTR reactor have positive correlation with the ammonium, nitrites and nitrates ions (R= 0.368, R=0.442 and R=0.362 respectively) and the samples of CH4-CSTR reactor have positive correlation only with TDS (R=0.860). Zebrafish correlates with phosphates (R= 0.542) and ammonium ions (R=0.562) for the samples of H2-CSTR, while for the samples of CH4-CSTR correlate with phosphates (R=0.963) and nitrites ions (R= 0.960). Daphnia magna does not show significant correlation. The highest values observed was for the samples of H2-CSTR with the ammonium ions (R= 0.316). According to the above results it is proved that Thamnocephalus platyurus and zebrafish are the most sensitive and suitable organisms for the toxicity estimation of the particular effluents. The observation of spinal malformations in a small percentage of zebrafish, led to the detection of heavy metals to all treated samples. Chromium, manganese, zinc and lead were detected, however the role of each one of them in the observed malformations could not be investigated in the frames of this study and further research is required. In ferentially, all the treated samples with both methods were toxic. They are not environmentally safe for direct disposal in the aquatic receiver and further treatment for the removal of the toxic factors as phosphates and the ions of nitrogen is needed. Finally, it must be noted that the present study is the first toxicity evaluation study of the dairy wastewaters after their treatment for biogas not only in the Greek area but worldwide. Since such a treatment constitutes an innovative and combined methodology that aims to the remediation of the wastewaters and the production of a beneficial by-product as biogas, the results of this study could constitute a useful tool, in one hand for the scientists concerning wastewater treatment provoking them to search methods for further remediation of these effluents from the remaining toxic factors and on the other hand for the officials in order to achieve monitoring and controlling of these particular units.

Made available in DSpace on 2014-10-09T12:46:40Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:48Z (GMT). No. of bitstreams: 1 08959.pdf: 6226672 bytes, checksum: d673a2d8ecb4902930cded5516338372 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP / FAPESP:99/05064-8

Orientador: Fábio Erminio Mingatto / Banca: Andréa Fontes Garcia / Banca: Sérgio Diniz Garcia / Resumo: Fipronil é um inseticida e acaricida altamente efetivo pertencente à família dos fenilpirazóis e ultimamente vem sendo extensivamente utilizado para combater infestações parasitárias tais como pulgas, formigas, cupins, carrapatos e piolhos de cães, gatos e bovinos. De acordo com relatos apresentados na literatura científica, existem casos de intoxicação hepática em mamíferos devido à sua exposição acidental ou utilização equivocada. O fígado desempenha função central no metabolismo, recebe nutrientes e xenobióticos que são por ele absorvidos, transformados, armazenados e liberados no sangue. A mitocôndria é responsável pela síntese de quase a totalidade do ATP necessário à manutenção da estrutura e função celular. Neste trabalho foram avaliados os efeitos do fipronil sobre a bioenergética de mitocôndrias isoladas de fígado de rato. Nas concentrações testadas (5 a 25 μM), o fipronil inibiu a respiração no Estado 3 da respiração em mitocôndrias energizadas com glutamato + malato, substratos do complexo I da cadeia respiratória, além de dissipar o potencial de membrana mitocondrial, acarretando a inibição da síntese de ATP pelas mitocôndrias. O efeito inibidor do fipronil sobre o complexo I foi confirmado pela inibição da atividade da enzima NADH desidrogenase. Esse efeito apresentado pelo fipronil sobre a bioenergética mitocondrial pode estar relacionado ao efeito tóxico apresentado pelo inseticida no fígado. / Abstract: Fipronil is a highly effective insecticide and acaricide that belongs to the phenylpyrazole chemical family and it has been extensively used to control fleas, ticks and lice of dogs, cats and bovines.As reported by literature, there are intoxication cases due to the accidental exposure or mistaken fipronil application in mammals, it might affect including the liver that performs essencial functions related to metabolism, due to the liver receives nutrients and xenobiotics that are absorbed, converted, stored and released into the blood. The mitochondria is responsible for almost entirety ATP synthase required to maintaining cellular structure and function. In this paper were evaluated the fipronil effects on bioenergetic of isolated rat-liver mitochondria. In the tested concentrations (5 to 25 μM), the fipronil inhibited State III of respiration to mitochondria energized with glutamate + malate, complex I substrates of respiratory chain, besides dissipate mitochondrial membrane potential, resulting in mitochondrial ATP synthase inhibition. The fipronil inhibitor effect about the complex I was confirmed by the inhibiting enzyme NADH dehydrogenase activity. The effect presented by fipronil about the mitochondrial bioenergetic may be related to the toxic effect showed by the insecticide on liver / Mestre

Orientador: Fábio Erminio Mingatto / Resumo: O imidacloprido (IMD) é um inseticida neonicotinóide largamente utilizado em diversas culturas agrícolas e em animais para o controle de pragas. O IMD é rapidamente absorvido pelo trato gastrointestinal e por contato, sendo rápida e uniformemente distribuído nos órgãos e tecidos. Dados da literatura mostram que as concentrações mais elevadas foram observadas nos órgãos de eliminação: fígado e rins. O fígado é o principal órgão envolvido na biotransformação de substâncias exógenas (xenobióticos), convertendo compostos hidrofóbicos em hidrossolúveis, mais facilmente eliminados pelo organismo. Vários estudos vêm sendo conduzidos sobre os efeitos tóxicos do IMD em animais, causando danos ao fígado. Nesse sentido, o objetivo desse estudo foi avaliar os mecanismos envolvidos na toxicidade do IMD sobre a bioenergética de mitocôndrias e hepatócitos isolados de rato e ações do IMD sobre o metabolismo de carboidratos e proteínas em fígado de rato em perfusão. Em mitocôndrias isoladas, o IMD promoveu uma diminuição dose-dependente no estado 3 da respiração e na produção de ATP, sem afetar o potencial de membrana mitocondrial. Experimentos subsequentes medindo o consumo de oxigênio mostraram que o IMD não afeta a cadeia respiratória e que seu efeito é semelhante ao da oligomicina (inibidora da FoF1-ATP sintase) e/ou ao do atractilosídeo (inibidor do translocador de nucleotídeos de adenina, ANT). IMD inibiu a atividade da FoF1-ATP sintase em mitocôndrias rompidas e inibiu parcialmente a d... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Protein misfolding diseases (PMDs) are a broad group of disorders including Alzheimer’s, Parkinson’s and prion diseases. They are characterised by the presence of aggregated, misfolded host proteins which are thought to cause cell death. Prion diseases are associated with misfolded prion protein (PrPSc), which has a tendency to form fibrillar aggregates. By contrast, Alzheimer’s disease (AD) is associated with misfolded amyloid beta (Aβ), which aggregates to form characteristic Aβ plaques. A feature which is common across PMDs is that small assemblies (oligomers) of the misfolded proteins are thought to be the important neurotoxic species, and it has been proposed that there may be a shared mechanism leading to cell death across PMDs caused by oligomers. In this study, the toxicity of different misfolded forms of recombinant PrP (recPrP) and recombinant Aβ (recAβ) and the mechanisms leading to cell death were investigated using a primary cell culture model. In addition, the importance of the disulphide bond in recPrP in relation to oligomer formation was explored using size exclusion chromatography and mass spectrometry, the toxicity of the different resulting oligomer populations were also investigated. Both recPrP oligomers and fibrils were shown to cause toxicity to mouse primary cortical neurons. Interestingly, oligomers were shown to cause apoptotic cell death, while the fibrils did not, suggesting the activation of different pathways. By contrast, recAβ fibrils were shown to be non-toxic to cortical neurons, Aβ oligomers, however, were shown to cause toxicity. Similar to recPrP, my data showed that it is likely that recAβ 1-42 oligomers also cause apoptosis. However, by contrast this seemed to be caused by excitotoxicity, which was not found to be the case for recPrP. Additionally, I have shown that the presence or absence of the disulphide bond in PrP has a profound effect on the size of oligomers which form. RecPrP lacking a disulphide bond leads to the formation of larger oligomers which are highly toxic to primary neurons. Findings from this study suggest that structural properties such as the disulphide bond in PrP can affect the size and toxicity of oligomers, furthermore, whilst oligomers have been shown to be important in both AD and prion diseases, they may not trigger the same pathways leading to cell death.

Orientador: Chung Man Chin / Banca: Leoberto Costa Tavares / Banca: Agnaldo Bruno Chies / Banca: Maria do Carmo Longo / Banca: Veni Maria Andres Felli / Resumo: A inflamação é uma reação de defesa e reparo fisiológico, importante em resposta a agressões físicas, químicas ou biológicas ao organismo, que geram o aparecimento dos quatro sinais cardinais dor, edema, calor, rubor, incluindo, muitas vezes a perda de função do tecido ou órgão. O processo inflamatório agudo é imediato e inespecífico contra o agente agressor, podendo evoluir para crônico, caso haja a permanência do agente agressivo e é caracterizado pelo aumento de celularidade e outros elementos teciduais. Várias substâncias estão envolvidas no processo inflamatório, como a prostaglandinas, histamina, serotonina e citocinas pró-inflamatórias como IL-1b, 1L-6, IL-8, TNF-a, NF-kB. Estima-se que exista na terapêutica, mais de 50 antiinflamatórios não esteróides (AINEs) diferentes, mas nenhum deles totalmente destituído de efeitos tóxicos, como a gastrotoxicidade, mesmo os compostos mais novos, seletivos para receptores COX2, como o celecoxibe. Por este motivo nenhum AINEs é recomendado para utilização em processos inflamatórios crônicos. Neste sentido, Vizioli (2006) e Castro (2008), planejaram pró-fármacos taurínicos e híbridos ftalimídicos, respectivamente, obtendo resultados promissores como antiinflamatórios potenciais destituídos de gastrotoxicidade. O presente trabalho visa realizar os testes pré-clinicos de atividade antiinflamatória aguda e crônica. Os resultados demostraram que que todos os derivados testados não apresentam gastrotoxicidade em relação ao padrão AINE testado, sem alteração significativa da resposta inflamatória aguda, com exceção do derivado de ibuprofeno N-(1,3-dioxo-1,3-diidro-2H-isoindol-2-il)-2-(4-isobutilfenil) propanamida, que demonstrou atividade inferior. Em estudo de atividade inflamatória crônica... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Inflammation is a defense and repair physiologic reaction important in response to an physical, chemical or biological aggression of the body, providing the appearance of the four cardinal signs of pain, swelling, heat, redness, including often the loss of function of the tissue or organs. The acute inflammatory process is immediate and nonspecific against the aggressive agent and it is characterized by increased cellular and other tissue elements. Series of substances are involved in the inflammatory process such as prostaglandins, histamine, serotonin and pro-inflammatory cytokines such as 1L-6, IL-8, a-TNF, NF- kB. It is estimated that exists more than 50 different non steroidal anti-inflammatory drugs (NSAIDs) drugs in the market, but none of them are wholly without side effects such as gastro toxicity, even the newer compounds, selective to COX2 receptors, as the celecoxib. For this reason none of NSAIDs is recommended for use in chronic inflammatory diseases. In this sense, Vizioli (2006) and Castro (2008), planned new taurine prodrugs and phtalimide hybride NSAIDs, respectively, showing promising results as anti-inflammatory without toxicity. This work aims to accomplish pre-clinical assay by acute and chronic models of inflammation. The results showed that all derivatives tested have no gastro toxicity when compared with the NSAIDs standard. No significant inflammatory response was observed with the exception toibuprofen derivative N-(1,3-dioxo-1,3-diidro-2H-isoindol-2-il)-2-(4-isobutilfenil) propanamide, which showed less activity. In the chronic inflammatory study activity all compounds phthalimide and taurine showed increase of activity compared to standard NSAIDs with decrease of the mortality and exclusion of the clinical signals such as bleeding, weight loss, and increased defecation rate... (Complete abstract click electronic access below) / Doutor

A number of pharmaceuticals have been shown to have adverse effects on key biological processes of aquatic organisms at low concentrations (ng/l range). Key questions for chemical risk assessment are whether such pharmaceuticals can produce adverse effects on organisms when present in the environment in combination and at low concentrations, whether these can be classified as additive, and under what circumstances can they be predicted. The main purpose of this study was to assess the potential for combination effects of a multicomponent steroid pharmaceutical mixture of dissimilarly acting compounds on an ecologically relevant end point – reproduction, using the existing predictive toxicity models Concentration Addition (CA) and Independent Action (IA). Concentrations of steroids close to those reported in the environment were shown to produce adverse effects on reproduction when present in combination with other steroids. Clear combination effects significantly larger than the effects of the individual compounds were observed when each compound was present at a concentration below the detection limit of the assay, demonstrating a ‘something from nothing’ mixture effect. Furthermore, IA predicted more pronounced effects on egg production that CA, an observation previously unreported from the literature. Actual observed effects were closer to the IA prediction. Additional biomarker and molecular endpoints were examined in subsequent studies to establish the mechanisms of disrupted reproduction in pair-breeding FHMs exposed to the steroid mixture. Results from this study indicate that reproductive impairment of fish exposed to the steroid mixture is likely due to the masculinisation of female fish due to the androgenic activity of the mixture. These results have implications for chemical risk assessment, and in particular, highlight the need for caution when using CA as a worst-case approximation of mixture effects.