O vírus de influenza aviária H5N1 tem se disseminado rapidamente por diversos países e continentes nos últimos anos, gerando grandes perdas econômicas e de vidas humanas. Existe a possibilidade de a doença chegar ao Brasil, o que provocaria elevado impacto sobre a economia, especialmente sobre o setor avícola. A ausência e a necessidade de estimativas de impacto econômico no país, derivadas de surtos de gripe aviária em território brasileiro, motivaram a presente pesquisa. Visando gerar tais estimativas e analisá-las, foram simulados três cenários utilizando-se de um modelo aplicado de equilíbrio geral inter-regional, denominado TERM-BR. O primeiro cenário (Cenário I) contempla um foco da doença no Rio Grande do Norte, região Nordeste do país. O segundo (Cenário II) simula a presença de diversos focos da doença no estado de São Paulo. O terceiro (Cenário III) considera o surgimento de diversos focos presentes nos estados Rio Grande do Norte, Rondônia, São Paulo e Rio Grande do Sul. Os resultados sinalizam impactos de maior dimensão na medida em que os focos da doença surgem próximos aos mercados produtores, exportadores e consumidores, como é o caso da região Sul e Sudeste. Na região Sul, em função da dimensão da avicultura na economia local, a crise do setor avícola acaba refletindo negativamente e acentuadamente sobre o conjunto da economia local. Nas regiões Norte e Nordeste, as restrições sobre a aquisição de aves vivas pelas famílias têm grande peso na retração da atividade econômica do setor avícola, já que a atividade de abate é pouco representativa e parcela importante das aves é adquirida diretamente pelas famílias, o que não acontece na mesma dimensão nas demais regiões do país. Observa-se também que o aumento do consumo de carne bovina e suína contribui para reduzir a crise na economia estadual nos estados produtores, e é também a fonte de crescimento para os estados em que a bovinocultura se destaca. O choque de demanda doméstica de produtos avícolas, comparado com os demais choques, revela-se como o principal responsável pelo comportamento na produção em quase todos os estados. Já a redução das exportações tem grande peso sobre o comportamento da produção avícola quando o foco da doença é na região exportadora ou próxima a ela. No estado de Santa Catarina, o choque de exportações prepondera sobre a queda do consumo doméstico quando do fechamento quase total dos mercados externos para carne de aves. Por último, o choque de oferta, via mortalidade das aves e destruição de ovos, pouco influencia a magnitude da queda na produção dos produtos da avicultura. / In the past few years, the bird flue virus H5N1 spread rapidly through various countries and continents, causing great economic and human losses. There is also the possibility of the disease arriving in Brazil, which would have a substantial impact on the country\'s economy, particularly on its poultry sector. The present study addresses the lack of estimates of the potential economic consequences of a bird flu outbreak on commercial poultry production in Brazil. The analysis consists of three simulations using a interregional general equilibrium model called TERM-BR. The first scenario focuses on an outbreak in the state of Rio Grande do Norte in the Northeastern part of the country. The second scenario simulates an outbreak at various places in the State of Sao Paulo, and the third scenario assesses the consequences of a bird flue outbreak in various states simultaneously, Rio Grande do Norte, Rondônia, São Paulo and Rio Grande do Sul. The results indicate greater economic impact when the outbreak occurs close to points of production and consumption, which is the case in the Southern and Southeastern regions of Brazil. In the South, where the poultry sector constitutes a larger share of the local economy, a potential avian flu outbreak will also have a greater negative economic impact. In the Northern and Northeastern region, live birds are generally purchased and slaughtered directly by individual families living in suburban and small town settings rather then by large scale processors and packinghouses. This characteristic explains why potential restrictions on these small purchases of live birds will have a very large negative economic impact on the poultry sector in the affected states. A possible reduction in poultry supply could however be offset by an increase in beef and pork consumption, thereby softening the economic affect of a bird flue outbreak by promoting growth of the beef and pork industry. In most states, this fall of domestic poultry demand is the primary cause for a shift in production. In contrast, the fall in export demand only weighs heavily on the local economy when the outbreak occurs close to exporting regions. In the state of Santa Catarina, for example, the effect of a fall in export demand dominates the effect of a fall in domestic demand, as export markets are almost completely shutdown. Finally, the reduction in poultry supply through death of infected birds and destruction of eggs, has little affect on the decrease of poultry production.

Orientador: Wanderley Dias da Silveira / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-21T23:45:44Z (GMT). No. of bitstreams: 1 Rojas_ThaisCabreraGalvao_D.pdf: 2609032 bytes, checksum: 23a0546c76c17eff8087d0160c69308d (MD5) Previous issue date: 2012 / Resumo: A bactéria Escherichia coli coloniza o trato intestinal de aves e humanos, de maneira comensal sem causar processos infecciosos. No entanto alguns clones adquiriram fatores de virulência específicos, permitindo o desenvolvimento de diferentes doenças como infecção do trato urinário, diarréia e meningite em humanos e colibacilose em aves. As linhagens que causam doença em aves são tipicamente denominadas APEC (Avian Pathogenic Escherichia coli). Neste trabalho foram sequenciados e anotados os genomas de quatro linhagens APECs (SCI-07, SEPT362, S17 e O8)que, juntamente com mais nove genomas referentes a linhagens de Escherichia coli patogênicas para aves e patogênicas para humanos foram utilizados para a busca de genes sob seleção positiva. Os genes homólogos foram agrupados,e posteriormente submetidos ao alinhamento de códons e das sequencias protéicas correspondentes. Uma árvore filogenética foi gerada para cada grupo de proteínas homólogas. Testes estatísticos determinaram qual entre os modelos de seleção neutra ou seleção positiva melhor explicou os dados existentes (alinhamentos de códons e árvores filogenéticas). Essas análises detectaram duzentas e cinquenta e quatro grupos de genes homólogos com evidência de seleção positiva. Para cada grupo foi realizado um teste de recombinação para verificar se o aumento na variação das sequencias não era devido à conversão gênica, resultando em cento e dezesseis grupos de genes homólogos sob seleção positiva. A proteína correspondente a um gene de cada grupo de genes homólogos foi identificada, por meio da ferramenta Blast. Diversos fatores de virulência, já conhecidos, e proteínas regulatórias puderem ser detectados. Os genes sob seleção positiva, também foram submetidos à anotação considerando o termo GO (Gene Ontology),apenas da categoria processo biológico. Dos cento e dezesseis genes apenas cinquenta e sete puderam ser identificados por meio dessa metodologia. O resultado da classificação dos genes dentro da classe GO, considerando o terceiro nível hierárquico,mostrou que a maioria dos genes anotados (31) tinha relação com o metabolismo primário.As proteínas cuja identificação, por meio do blast, não foi possível (proteínas hipotéticas)foram submetidas à análise de predição de localização subcelular e de peptídeo sinal. Essas análises revelaram que três proteínas desconhecidas (hypothetical proteinECIAI39_1028, hypothetical proteinZ0639e hypothetical proteinEC042_3791) são potenciais alvos para estudos que visam à busca de novos fatores de virulência de Escherichia coli patogênicas / Abstract: The bacterium Escherichia coli colonizesthe intestinal tract of birds and humans, in a commensal relationship without causing infection. However, some clones have acquired specific virulence factors allowing the development of various diseases such as urinary tract infection, diarrhea and meningitis in humans and colibacillosis in poultry. The strains that cause disease in birds are typically named APEC (Avian Pathogenic Escherichia coli). In this study we sequenced and annotated the genomes of four APECs strains (SCI-07, SEPT362, S17 and O8). These genomes and nine others avian pathogenic Escherichia coli and humans pathogenic strains genomes were used for studying genes under positive selection. The homologous genes were grouped and then subjected to codons and corresponding protein sequences alignment. A phylogenetic tree was generated for each group of homologous proteins. Statistical tests determined which among neutral or positive selection models best explains the existing data (codon alignments and phylogenetic trees). This analyzes detected two hundred fifty-four groups of homologous genes with positive selection evidence. For each group a recombination test was conducted to verify if the variation increase in the sequences was not due to gene conversion, resulting in one hundred and sixteen groups of homologous genes under positive selection. The protein corresponding to a gene of each group of homologous genes under positive selection was identified through Blast tool. Genes under positive selection were annotated considering the GO term (Gene Ontology), just for the biological process category. Only fifty-seven genes could be identified using this methodology. The gene classification within the GO classes, considering only the third hierarchical level showed that most of the annotated genes (31) were related with the primary metabolism. Proteins which blast identification was not possible (hypothetical proteins) were subjected to sub cellular localization and signal peptide prediction analyzes. These analyzes revealed that three unknown proteins (hypothetical protein ECIAI39_1028, hypothetical protein Z0639e hypothetical protein EC042_3791) are potential targets for studies, in order to search for new virulence factors of pathogenic Escherichia coli / Doutorado / Microbiologia / Doutora em Genética e Biologia Molecular

Avian influenza is an infectious disease of birds caused by the Type A strain of the influenza virus. The disease, which was first identified in Italy more than 100 years ago, occurs worldwide (World Health Organization, 2006a). The current outbreak of the highly pathogenic avian influenza A (H5N1), which began in Southeast Asia in mid-2003, is the largest and most severe on record. Never before in the recorded history of this disease have so many countries been simultaneously affected. Since the last pandemic in 1968-1969, the risk of an influenza pandemic has not been considered greater than at the present time. The importance of intervention strategies had become increasingly evident throughout the world. The World Health Organization provides a generic outline for preparedness plans to assist countries in their preparations to respond to a possible avian influenza pandemic. These guidelines may be modified as the epidemiology of avian influenza evolves. The South African National Department of Health has developed national guidelines in the form of an avian influenza preparedness plan. These draft guidelines do not provide detailed Environmental Health work methods and - procedures for the effective surveillance and control of the disease. The general purpose of this study is to develop a standardised set of Environmental Health work methods and - procedures, which will contribute to the effective surveillance and control of avian influenza in the Eastern Cape province – South Africa. Within the context of the purpose of this study, a qualitative, explorative, descriptive, inductive and deductive research design will be used. The methods of data collection will be documentary research, telephonic as well as in-depth personal interviews. In this study, documentary research will be the primary method of data collection. With a qualitative approach, the researcher will be the human instrument for data analysis. The process of qualitative data analysis will be based on data reduction and interpretation; and will be conducted as an activity simultaneously with data collection, data interpretation and narrative reporting writing.

Les moustiques jouent un rôle essentiel dans la dynamique de transmission du paludisme. Plusieurs traits d’histoire de vie de ces insectes hématophages vont, en effet, intervenir dans le calcul du taux reproductif de base du parasite. Parmi eux, la probabilité et l’intensité d’infection des vecteurs, suite à la prise d’un repas de sang infectieux, sont des facteurs primordiaux pour la transmission de Plasmodium. Pourtant, au sein d'une même population, une réelle hétérogénéité d’infection des moustiques a été observée: alors que certain ne sont pas infectés, que d'autres le sont faiblement, une partie des vecteurs vont présenter des taux d'infection extrêmement forts. Identifier les sources de variations responsables de cette hétérogénéité est indispensable pour comprendre la dynamique de transmission de Plasmodium. Certains paramètres d’origine génétique et environnementale, tel que la température et la nutrition, ont déjà clairement été identifiés comme ayant un impact sur le taux d’infection des moustiques. Néanmoins, de nombreux facteurs restent encore à explorer. En utilisant un système expérimental composé du parasite de la malaria aviaire Plasmodium relictum, de son vecteur naturel le moustique Culex pipiens et de l’un de ses hôtes vertébrés Serinus canaria, nous nous sommes intéressés aux effets de certains de ces paramètres, peu pris en compte jusqu’à présent, sur l’infection des moustiques. Nous avons notamment pu mettre en évidence des conséquences importante de l’infection parentale, de l’âge des vecteurs, ainsi que de leur fond génétique. Parallèlement, nous nous sommes intéressés à un facteur souvent laissé de côté, l’effet « hôte vertébré » sur l’infection des moustiques. Dans cette dernière partie, on a pu observer que la dynamique d’infection du parasite au sein de l’hôte influence de manière importante le taux de transmission de Plasmodium. Les sources d’hétérogénéité d’infections des moustiques sont donc multiples et l’ensemble des membres de cette association tripartite hôte/parasite/vecteur vont pouvoir influencer de manière importante la dynamique de transmission du parasite. / Mosquitoes play a key role in the dynamics of malaria transmission. Indeed, several life history traits of these bloodsucking insects are closely associated with the basic reproductive rate of the malaria parasite. One of the most important parameters for the transmission of Plasmodium is the rate and intensity of the mosquito infection. However, within a single population, a great heterogeneity of mosquito infection levels is often observed: some mosquitoes are not infected, others are only weakly infected, and yet others have extremely high infection rates. Identifying the sources of variation responsible for this heterogeneity is essential in order to understand the transmission dynamics of Plasmodium. Certain genetic and environmental (temperature, nutrition) parameters have already been identified as having an impact on mosquito infection rates. Nevertheless, many factors remain to be explored. Using an experimental system composed of the avian malaria parasite Plasmodium relictum, its natural vector Culex pipiens and one of its vertebrate host Serinus canaria, we have investigated the effect of several seldom investigated parameters on the infection of mosquitoes. We observed surprising effects of the effect of parental infection, mosquito age and genetic background. In parallel, we also studied a rarely investigated parameter: the impact of the vertebrate host on the mosquito infection rate. We showed that parasite infection dynamics within the host, at short but also long time scales, significantly influence the transmission of Plasmodium to the vector. The sources of heterogeneity of mosquito infection are therefore multiple and all members of this tripartite partnership (i.e. host / parasite / vector) are able to significantly influence the transmission dynamics of the parasite.

I studied the spatial distribution of South African avian species richness from the viewpoint that humans are a substantial modifying force on earth, and have also modified the historical spatial distribution of species richness. The main aim of the thesis is to investigate the way in which humans have modified avian species richness patterns in South Africa at the quarter-degree square (QDS) resolution, which is a phenomenon that has been either overlooked, or not completely clarified, in many previous studies of the same region and data at the same resolution. In particular, I investigated hypotheses that were proposed to explain the maintenance of a positive relationship between native species richness and human population density in the face of negative human impacts. Further, I investigated which of the possible anthropogenic and natural environmental factors determine spatial distribution in exotic bird species. Highlighted from these studies are that substantial positive and negative human influences on bird species richness distribution patterns are observable at the QDS resolution, that there are differences between common native birds and rare native birds with regard to their relationships with anthropogenic environmental conditions and exotic bird species, and that the particular combination of environmental covariates that is important for the spatial distributions of exotic species is taxon- and scale-dependent. Even though these results have contributed much towards our understanding on how human modifications have affected species richness patterns, this thesis leaves some unanswered questions. Finer resolution studies and temporal studies are needed to examine many of these questions. Further, an interdisciplinary approach incorporating politics and economics into ecological studies is needed to enhance our understanding of the factors that modify the distribution of humans and their associated threats and benefits to species richness. / Dissertation (MSc)--University of Pretoria, 2010. / Zoology and Entomology / unrestricted

The aim of this study was to develop a standardised set of Environmental-Health work methods and procedures, with the purpose of contributing to the effective surveillance and control of Cholera in the KwaZulu-Natal province, South Africa. The researcher followed a qualitative research design, which was explorative, descriptive, inductive and deductive by nature. The methods of data collection were documentary research and focus-group interviews. A documentary research approach was employed as the primary method of data collection for the study. The researcher has used semi-structured questions to obtain relevant information from the participants in the focus groups. The purpose of using semi-structured questions in the focus groups was to draw on their knowledge and experience of communicable disease surveillance and control in relation to Cholera, as well as to ascertain their views on the role of the Environmental-Health Practitioners in the Communicable - Disease Outbreak- Response Teams at the three different spheres of government. The process of qualitative data analysis was followed. This was based on data reduction and interpretation; and it was conducted as an activity simultaneously with data collection, data interpretation (coding) and narrative writing. The information obtained from the analysed data assisted in the development of the environmentalhealth work methods and procedures for the surveillance and control of Cholera in the KwaZulu-Natal province, South Africa. In this study, firstly, the epidemiology of Cholera was described and analysed against the background of its manifestation in South Africa. Secondly, the national health care system, with specific reference to the place and role of environmental health practitioners at national, provincial and municipal spheres – in relation to Cholera surveillance and control – was analysed. Thirdly, the relevant research that has been done globally has been analysed against the background of the findings of the above, together with work methods and procedures to be used by environmental-health practitioners during the surveillance and control of Cholera in the KwaZulu-Natal Province, South Africa. These include, inter alia: Work methods and procedures for Cholera case investigation; Work methods and procedures for sanitary investigations; and Work methods and procedures for identifying the sources of contamination in environmental waters. Finally, the conclusion and limitations was presented, and appropriate recommendations were made. These include: he need to educate all role - players, on the recent developments in the identification of Vibrio cholerae from environmental surface waters; Communication systems should be developed that allow the Director: Environmental Health to communicate urgent environmental health information directly to the Minister of Health; he training of environmental-health practitioners on detailed work methods and procedures for the surveillance and control of Cholera; and the existing national Cholera control guidelines need to be updated to include relevant environmental health situations when emergencies arise.

The species–area relationship (SAR) has been applied to predict species richness declines as area is converted to human-dominated land covers.In many areas of the world, however, many species persist in human-dominated areas, including threatened species. Because SARs are decelerating nonlinear, small extents of natural habitat can be converted to human use with little expected loss of associated species, but with the addition of more species that are associated with human land uses. Decelerating SARs suggest that, as area is converted to human-dominated forms, more species will be added to the rare habitat than are lost from the common one. This should lead to a peaked relationship between richness and natural area. I found that the effect of natural area on avian richness across Ontario was consistent with the sum of SARs for natural habitat species and human-dominated habitat species, suggesting that almost half the natural area can be converted to human-dominated forms before richness declines. However, I found that this spatial relationship did not remain consistent through time: bird richness increased when natural cover was removed (up to 4%), irrespective of its original extent. The inclusion of metapopulation processes in predictive models of species presence improves predictions of diversity change through time dramatically. Variability in site occupancy was common among bird species evaluated in this study, likely resulting from local extinction-colonization dynamics. Likelihood of species presence declined when few neighbouring sites were previously occupied by the species. Site occupancy was also less likely when little suitable habitat was present. Consistent with expectations that larger habitats are easier targets for colonists, habitat area was more important for more isolated sites. Accounting for the effect of metapopulation dynamics on site occupancy predicted change in richness better than land cover change and increased the strength of the regional richness–natural area relationship to levels observed for continental richness–environment relationships suggesting that these metapopulation processes “scale up” to modify regional species richness patterns making them more difficult to predict. It is the existence of absences in otherwise suitable habitat within species’ ranges that appears to weaken regional richness–environment relationships.

Defence sounds are widespread and diverse amongst insects. Despite their ubiquity and variability, hypotheses explaining their functions and evolutionary origins have been understudied. My thesis focused on these topics using silk and hawkmoth Bombycoidea caterpillars as a model system. In Chapter Two I investigated why defence sounds have evolved in some caterpillars but not others by testing the hypothesis that large body size is a factor in the evolution of defence sounds. To test this hypothesis, I followed the development of defence sounds in four Bombycoidea species from hatching to pupation. I predicted that early instars would not produce defence sounds, and that within sound producing instars defence sounds would be more likely to occur in larger caterpillars. Results showed that defence sounds were absent in the first and second instar, and that they developed in the third through to the fifth instar in all species. Moreover, the onset of sound production occurred when all species were the same relative size (~1.12 g, ~26.37 mm), despite the fact that the species differed in their final instar size. I concluded that early instar caterpillars do not make defence sounds, and that there is a critical size when defence sounds develop. I further tested the hypothesis that smaller caterpillars do not have enough energy to make defence sounds, by analyzing the relationship between size and several temporal characteristics of the sounds. I predicted that smaller caterpillars would signal less than larger caterpillars, and produce shorter signal units and trains, with lower duty cycles. Results partly supported the hypothesis, showing that in two species there was a positive relationship between size and the number of units produced within two seconds following an attack, the mean number of units per train, and the mean duration of the units in one species. I also tested the hypothesis that sounds of small caterpillars are not in the hearing range of predators. I predicted that there would be a relationship between caterpillar size, and the sound pressure levels and dominant frequencies of the sounds. Results showed no significant relationships with dominant frequencies or sound pressure levels and size. I concluded that the caterpillars made sounds that were within the hearing range of major predators from the onset of sound production. In Chapter Three I followed the other antipredator defences of the four species throughout development. I investigated whether the frequency of defences changed with instar. I found that the caterpillars employed up to seven different secondary defences throughout development. In one species the frequency of dropping and major thrashing increased in the late instars, and in a different species the frequency of regurgitation increased. I concluded that in some cases defence sound production accompanies other secondary defences that increase with the size of caterpillars during development. In Chapter Four I tested the hypothesis that the defensive whistle of the walnut sphinx caterpillar, Amorpha juglandis (Sphingidae: Sphinginae), functions to startle birds. I predicted that the birds would startle to the sounds, and habituate upon repeated exposure within a trial. Results showed that play-back recordings of the whistles elicited a startle response in captive red-winged blackbirds (Agelaius phoeniceus) and caused them to hesitate and/or flee from prey. I concluded that the whistles function as a startle display. Together, the experiments conducted within my thesis addressed important outstanding questions regarding the evolutionary origins of defence sounds in caterpillars, and their functions in predator-prey interactions.

Avian influenza is a contagious viral disease caused by influenza virus type A. Avian influenza can be disastrous (if it occurs), due to the short incubation period (about 1--4 days). Thus it is important to study this disease so that we are more prepared to manage it in the future. A classical system of differential equations (the half-saturated incidence model) and three Filippov models --- an avian-only model with culling of infected birds, an SIIR (Susceptible-Infected-Infected-Recovered) model with quarantine of infected humans and an avian-only model with culling both susceptible and infected birds --- that are governed by ordinary differential equations with discontinuous right-hand sides (i.e., differential inclusion) are proposed to study the transmission of avian influenza. The effect of half-saturated incidence is investigated, and the outcome of this model is compared with the bilinear incidence model. Both models remain endemic whenever their respective basic reproduction numbers are greater than one. The half-saturated incidence model generates more infected individuals than the bilinear incidence model. This may be because the bilinear incidence model is underestimating the number of infected individuals at the outbreak. For the Filippov models, the number of infected individuals is used as a reference in applying control strategies. If this number is greater than a threshold value, a control measure has to be employed immediately to avoid a more severe outbreak. Otherwise, no action is necessary. We perform dynamical system analysis for all models. The existence of sliding modes and the flow on the discontinuity surfaces are determined. In addition, numerical simulations are conducted to illustrate the dynamics of the models. Our results suggest that if appropriate tolerance thresholds are chosen such that all trajectories of the Filippov models are converging to an equilibrium point that lies in the region below the infected tolerance threshold or on the discontinuity surface, then no control strategy is necessary as we consider the outbreak is tolerable. Otherwise, we have to apply control strategies to contain the outbreak. Hence a well-defined threshold policy is crucial for us to combat avian influenza effectively.

Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) are added to polyurethane foams in a variety of industrial and consumer products to prevent flame ignition. The gradual release of these flame retardants (FRs) from such products leads to contamination of various abiotic and biotic media, including wild birds. Recent studies demonstrated endocrine-disrupting effects of TCPP and TDCPP, including alteration of circulating thyroid hormone (TH) levels. The TH-pathway is essential for normal growth and development in birds. There are limited data on the toxicological effects of TCPP and TDCPP in avian species and, prior to this work, no study has examined their effects in avian embryos. This M.Sc. thesis investigates the developmental, molecular and biochemical effects of TCPP and TDCPP in chicken (Gallus gallus domesticus) embryos via egg injection studies. TCPP delayed pipping at doses ≥9.24 μg/g, both TCPP and TDCPP reduced embryo growth at the highest dose (51.6 μg TCPP/g and 45 μg TDCPP/g), and TDCPP decreased free plasma thyroxine and gallbladder size at 7.64 μg/g and 45 μg/g, respectively. Real-time reverse transcription polymerase chain reaction was used to measure changes in mRNA levels of hepatic genes that were responsive to these FRs in a previous in vitro study. TCPP dysregulated the expression of TH-responsive genes and xenobiotic metabolizing enzymes (cytochrome P450s; CYPs), whereas TDCPP only affected CYPs. Less than 1% of the administered TCPP or TDCPP was detected in egg contents following 19 days of incubation, indicating extensive metabolism of the parent compounds. DNA microarrays were used to perform a global transcriptional analysis on liver samples from embryos that exhibited adverse effects following TDCPP injection. 47 differentially expressed genes were identified at the 45 μg/g dose. Functional analysis revealed that immune function and lipid and steroid metabolism were major targets of TDCPP toxicity and indicated a state of cholestatic liver/biliary fibrosis. Since the TH-pathway is a key regulator of metabolic homeostasis, its disruption early in development is a potential cause of the observed adverse effects. This thesis demonstrates, for the first time, developmental and endocrine-disrupting effects of TCPP and TDCPP in an avian species and attempts to link phenotypic changes to molecular-level disruptions in hopes to improve the understanding of their modes of action.