This work is focused on verification of p-Nitrotoluenu toxicity and compounds resulting from the aerobic transformation, and methyl group oxidation and reduction of nitro. Some of these products are not commercially available and had to be made soon. Toxicity of the substances was determined by toxicity tests. Were tested root growth inhibition Sinapis alba, which resulted in an inhibitory concentration IC50; test inhibition duckweed Lemna minor , which was also the determination of IC50 inhibitory concentration, and acute toxicity test Artemia salina, which was observed in mortality and immobility organisms and the test result was an efficient concentration EC50 value. Results of tests are compared in the conclusion of the work and is made evaluation of the toxicity of individual substances.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. There are numerous studies reporting developmental cardiac toxicity in multiple fish species due to PAH exposure. However, there are relatively few instances where the effects of acute PAH exposure in adult fish have been characterized. Furthermore, the majority of experiments comparing PAH toxicity with exposure route in adult fish focus on CYP1A gene expression or enzyme activity, while there is a lack of information about the possible pathophysiological effects. Therefore, the overall objective of this thesis was to characterize the sublethal effects of benzo[a]pyrene (BaP), a prototypical PAH, on adult zebrafish (Danio rerio) cardiorespiratory function and fitness following acute exposure by two different routes. In the first experiment, adult zebrafish were intraperitoneally (i.p.) injected twice (one injection/24 hr) with increasing concentrations of BaP (0.1, 10, and 1000 μg/kg) and compared to corresponding dimethylsulfoxide (DMSO) controls. In a second set of experiments, adult zebrafish were aqueously exposed to BaP (static, renewal at 24 hr; 16.2 and 162 μg/L) and compared to DMSO controls. Following 48 hr exposure, one group of fish (n=10/treatment group) were subjected to swimming performance tests to assess critical swimming speed (Ucrit), oxygen consumption rate (MO2), cost of transport (COT), standard metabolic rate (SMR), active metabolic rate (AMR), and factorial aerobic scope (F-AS). Another group of fish (n=12/treatment group) were subjected to echocardiography following 48 hr BaP exposure to evaluate cardiac function. Following echocardiography analysis, samples were collected for parent compound (BaP) body burden and CYP1A mRNA induction analysis. 48 hr BaP injection resulted in significant sublethal effects on adult zebrafish cardiorespiratory function. Oxygen consumption (MO2) was increased at three swimming speeds in injected BaP groups compared to control. In contrast, aqueously BaP-exposed fish showed increased MO2 only at the single lowest swim speed. COT was also similarly increased for both exposure routes. SMR was elevated with both exposure routes, while AMR remained unchanged. This resulted in a significant decrease in F-AS for all treatment groups compared to corresponding controls with both exposure routes. Cardiac function was significantly affected by both routes of BaP exposure. Ventricular heart rate was significantly decreased in BaP-exposed fish, both injected and aqueously-exposed. However, stroke volume was decreased only in fish aqueously exposed to BaP, which resulted in significantly reduced cardiac output with that exposure route. In contrast, the ratio of atrial to ventricular heart rate (AV ratio) was increased only in fish i.p. injected with BaP, indicating the possibility of cardiac arrhythmias occurring. Analysis of BaP body burdens in fish tissue allowed for identification of an overlapping dose group between exposure routes, through which comparisons of cardiotoxicity were then made. This comparison revealed slight differences in cardiotoxicity between exposure routes. BaP-injected fish suffered from more severe bradycardia than aqueously exposed fish. Furthermore, cytochrome P4501A (CYP1A) mRNA levels in liver and heart tissue showed more significant increases in injected fish, while skeletal muscle CYP1A was increased only following aqueous exposure. In conclusion, acute BaP exposure caused metabolic alterations and impaired cardiorespiratory function in adult zebrafish regardless of exposure route. Interestingly, the primary mechanism behind these effects appeared to differ slightly with exposure route. These results suggest that acute BaP exposure may have negative effects on adult fish survivability in the environment. Overall, this work provides valuable insight into the pathophysiogical consequences of acute PAH exposure in adult stage fish.

Indian Childhood Cirrhosis (ICC) is associated with excessive copper ingestion and hepatic deposition, is preventable by preventing copper ingestion and is partially treatable by copper chelation. However, copper administration causes only minimal hepatic damage in the rat and an acute rather than chronic liver injury in sheep. The hypothesis is explored that a second hepatic insult is synergistic with copper in causing cirrhosis. D-galactosamine was administered, to control rats and to rats orally dosed with copper acetate, to induce an acute hepatic injury documented by serum transaminases and liver histology. Surprisingly, copper-dosed rats (liver copper 607+129 ug/g, controls 48+7) were resistant to galactosamine-induced injury. Oral copper reduced the quantitative faecal anaerobical1y cultured bacterial count, suggesting that reduction in gut-derived portal vein endotoxin may explain the protective effect. Using the carbon tetrachloride model, copper again ameliorated, rather than aggravated, the hepatic injury. Impaired prostaglandin or leukotriene synthesis are discussed as possible mechanisms. To evaluate a possible disorder of copper transport in ICC, copper distribution amongst human serum proteins was investigated. In normal adults, copper was associated with caeruloplasmin (71+4%), "transcuprein" (7+2%), albumin (19+4%) and with amino acids (2+3%). Caeruloplasmin and caeruloplasmin-copper concentrations were low in neonates and symptomatic Wilson's disease. In contrast to the neonate, Wilson's disease exhibited raised total serum copper and non-caeruloplasmin-copper. In ICC, serum levels of caeruloplasmin and caeruloplasmin-copper were normal, but transcuprein- and albumin-bound copper were elevated. Raised concentrations of non-caeruloplasmin-copper in ICC and Wilson's disease perhaps represent overspill into the serum from a copper-laden liver. In serum from children with malignancy, copper and caeruloplasmin concentrations were high as previously reported. Unexpectedly transcuprein- and albumin-bound copper were also markedly elevated. It is to be determined whether this results from tissue catabolism of caeruloplasmin or from increased hepatic caeruloplasmin synthesis and copper turnover. Caeruloplasmin gene expression was investigated in adult and neonatal rat liver, to determine whether the copper profile seen in neonates results from a pre-translational defect in caeruloplasmin synthesis. Detection of mRNA in samples of Northern blotted polyadenylated RNA, using a 32P-labelled caeruloplasmin cDNA probe, demonstrated that the mRNA species isolated from the neonates was not different from that in the adults, with an apparent size of 4400 nucleotides. A reduced mRNA detection in neonatal rats was also shown. Whether this was sufficient to account for the diminished total serum copper and caeruloplasmin oxidase activity is not understood.

NPs are toxic to a wide range of organisms across trophic levels; gram-positive and gram-negative bacteria (Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and Escherichia coli), algae (Pseudokirchneriella subcapitata), crustaceans (Daphnia magna and Thamnocephalus platyurus), fish (rainbow trout, zebrafish, trout) and plants (Lactuca sativa L. and Raphanus sativus L). Due to their lack of target specificity, NPs may pose an environmental risk. The antibacterial properties of Ag and Cu nanoparticles (NP) are enhanced by their large reactive surface area, compared to bulk counterparts. Toxicity of NPs is attributed to their solubility and subsequent release of ions. However, the cytotoxic effects of NPs cannot always be attributed to the free ion fraction. The underpinning objective of this study was to link the response of microbial biosensors to detailed chemical analysis of NP dissolution products. NPs were suspended in Millipore water and in the presence of the steric stabiliser Na citrate and the resulting NP solubility characterised. Using chemical analysis this study quantified the flux of total dissolved metal (total [M]) and free metal ions [M+] from Ag and Cu NPs (Chapter 3). Two bioluminescent biosensors were used to assess the bioavailable metal fraction ([M]bio) of NP dissolution (Chapters 5 and 6). E. coli HB101 pUCD607 (bacterial) and M. citricolor (fungal) were chosen to represent NP toxicity across trophic levels using the same response mechanism. Additionally, the metal-induced bioreporter, P. fluorescens DF57-Cu15, was used to quantify the Cu bioavailability of Cu NP dissolution. By combining chemical and biological analysis this study inferred NP toxicity is not mass dependent, toxicity is dissolution dependent. Dissolution of Ag and Cu NPs in Millipore water was mostly in the [M+] form. This remained the case for Ag NPs in the presence of Na citrate. However, dissolution of Cu NPs in Na citrate was mostly as total [Cu]. This was due to Cu ions complexing readily with citrate. Toxicity of Ag NP dissolution in Millipore water was concentration dependent. Total [Ag] correlated with E. coli HB101 toxicity response. The addition of Na citrate reduced Ag NP dissolution and therefore reduced toxicity to E. coli HB101. M. citricolor was less sensitive than E. coli HB101 to the dissolution products of Ag NPs in Millipore water. However, the sensor was more sensitive to the dissolution of Ag NPs in Na citrate than E. coli HB101. Cu NPs were chemically stable in Millipore water. The bioreporter P. fluorescens DF57-Cu15 was not induced by Millipore suspensions and E. coli HB101 was not inhibited. However, M. citricolor responded to [Cu]bio of Millipore suspensions with a maximum 54% inhibition of bioluminescence. P. fluorescens DF57-Cu15 was induced by the dissolution products of Cu NPs with the addition of Na citrate, only at high NP concentrations (> 500 mg/L). [Cu]bio of the Na citrate suspensions was toxic to E. coli HB101. However, toxicity was greater for M. citricolor with a maximum biosensor inhibition of 83%. There was no correlation between total [Cu], [Cu2+] or [Cu]bio with the response of either biosensors nor the bioreporter. Interpretation of Ag and Cu NP toxicity was made possible by the combining of chemical and biological toxicity assessment. Dissolution of Ag NPs suspended in Millipore water could be attributed as the main factor in toxicity to E. coli HB101 because of the knowledge gained by chemical analysis. It also allowed the conclusion that NP dissolution was a key factor to toxicity in all cases but biological assessment attributed NP assimilation as a contributing factor. Biological assessment is vital as no chemical analysis can quantify [M]bio, especially when [M]bio was perceived differently by biosensors of different trophic levels and modes of action. Combining chemical and biological assessment in this study was essential for interpreting NP toxicity.

The pharmacokinetics of a range of substituted benzyl -cyclopropane-l-carboxylates topically applied in acetone to adult mustard beetles, Phaedon cochleariae, and in Sirius mineral oil to larval Spodoptera littoralis were investigated with particular reference to tissue binding and distribution. A set of pyrethroids with a wide range of binding properties was applied to adult mustard beetles. The form of the pharmacokinetic profiles was obtained by exhaustive soxhlet extraction of the tissues. Binding varied with the physicochemical properties of the compounds. Two phases of binding were identified; rapid binding to cuticle occured within seconds of topical application, followed by a slower binding which proceeded to a maximum after several hours. When cypermethrin was applied to larvae of S. littoralis, two similar phases were observed; rapid binding which took place over the first hour was followed by a slower binding which continued at a constant rate for up to 72 hours after dosing. Increasing the viscosity of the carrier oil reduced the rate of penetration of cypermethrin into larvae of S. littoralis. The tissue concentration of cypermethrin when equilibrated throughout the larval tissues was related to the ratio of tissue solids to tissue water. This suggests that the distribution of insecticide in the tissue is determined by partition processes. All of the tissues without exception reached steady state within one hour of dosing and the tissue levels maintained thereafter. However, this pattern was not observed for the gut contents, where cypermethrin levels reached a peak after six hours. Thereafter cypermethrin disappeared - from the gut, presumably as material was eliminated or degraded. The gut appears to be the only important site of loss of cypermethrin from Spodoptera larvae. The toxicological implications of these results are discussed.

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