As anfetaminas compreendem uma série de compostos com estrutura química semelhante à feniletilamina e que apresentam atividade estimulante do sistema nervoso central. Além de substâncias anorexígenas como o femproporex e a dietilpropiona, também estão incluídas nessa classe drogas ilícitas como a metanfetamina (ice, speed) e a metilenodioximetanfetamina (MDMA, ecstasy). Essas substâncias apresentam grande potencial de abuso, podendo ser utilizadas por diversos grupos sociais como motoristas profissionais (onde são conhecidas por \"rebite\"), estudantes, jovens (utilizando ecstasy em festas denominadas \"raves\") e pessoas que abusam de moderadores de apetite para o controle de peso. Interessantemente, há também a possibilidade de alguns indivíduos utilizarem anfetaminas em associação com benzodiazepínicos. Embora a comercialização dos derivados anfetamínicos tenha sido proibida no Brasil desde 2011, é de conhecimento que algumas pessoas ainda utilizam anorexígenos e recorram ao uso concomitante com benzodiazepínicos como forma de controlar a insônia provocada pelas anfetaminas. Outra situação de uso das duas substâncias ao mesmo tempo seria a de motoristas profissionais, usuários de \"rebite\", que também tentariam controlar os ciclos de sono utilizando benzodiazepínicos. Em vista dessa situação, seria interessante o monitoramento do uso desses grupos de fármacos através de análises toxicológicas. As análises toxicológicas convencionais (realizadas sobremaneira em sangue e urina) geralmente fornecem uma pequena janela de detecção, o que faz com que o uso intermitente possa não ser detectado. Quando se deseja informação de uso em longo prazo ou ainda sobre os padrões de uso de determinada droga, a matriz mais eficiente para realização das análises é o cabelo. No presente projeto, métodos analíticos foram desenvolvidos visando a detecção de fármacos da classe das anfetaminas (anfetamina, metanfetamina, MDMA, MDA e femproporex) e benzodiazepínicos (diazepam, nordiazepam, clordiazepóxido, oxazepam, clonazepam e temazepam) em amostras de cabelo. A microextração em fase líquida (LPME) e a extração em fase sólida (SPE) foram utilizadas como técnicas de preparação de amostras. Os analitos de interesse foram identificados por cromatografia em fase gasosa acoplada à espectrometria de massas (GC-MS). Após o desenvolvimento, otimização e validação, os métodos foram aplicados em amostras reais de voluntários suspeitos de utilizar alguma das substâncias em estudo, provenientes de um centro para tratamento de dependência química. Os resultados obtidos com a aplicação dos métodos mostraram sua eficácia para o fim que se destinam. / Amphetamines are a class of compounds with chemical structures similar to phenylethylamines that present stimulant activity in the central nervous system. Anorectic drugs such as fenproporex and diethylpropion and some illicit drugs as methamphetamine (ice, speed) and metilenodioximetamphetamine (MDMA, ecstasy) are also included in this class. These substances have a high abuse potential, and they can be used by various social groups, for example, professional drivers (who call them \"rebites\"), young students (using ecstasy in \"rave\" parties) and people who abuses anorectics to weight control. Interestingly, there is also a possibility of some people using anorectics and benzodiazepines in association. Although the commercialization of amphetamine derivatives has been recently banned in Brazil (2011), it is known that some people still use anorectic drugs and benzodiazepines to control insomnia induced by amphetamines. Another case of concomitant use would be professional drivers, who use \"rebites\", which also try to control their sleep cycles using benzodiazepines. Because of this situation, it would be interesting to monitoring the use of these drugs by toxicological analysis. The conventional toxicological analyses (performed in most cases in blood and urine) generally provide small window detection. In this case, intermittent drug use may not be detected. When long term information about drug use is needed, the most efficient matrix to carry out the analysis is hair. In this project, analytical methods were developed for the determination of amphetamines (amphetamine, methamphetamine, MDMA, MDA and fenproporex) and benzodiazepines (diazepam, nordiazepam, chlordiazepoxide, oxazepam, clonazepam and temazepam) in hair samples. Liquid-phase microextraction (LPME) and solid phase extraction (SPE) were used as sample preparation techniques in these methods. Analites were identified by gas chromatography/mass spectrometry (GC-MS). After the development, optimization and validation, the methods were applied in hair samples collected from patients of a drug rehabilitation clinic. The results obtained with the application of the developed methods showed their efficacy for the intended purpose.

Foram desenvolvidos métodos de determinação de urina e trítio em urina. Para o urânio foi adaptada a técnica de análise por fluorimetria em meio sólido. O limite de sensibilidade foi de 5. 10-4µg U/0,1 ml e o erro foi de cerca de 10% para concentrações em torno de 0,05 µg U/0,1 ml. Foi padronizado para o trítio o método de análise por cintilação em meio líquido. O método determina quantidades de trítio até pelo menos 8,10-3µCi/ml e o erro foi de cerca de 4% para concentrações de trítio em torno de 0,34 µCi/l. Depois de adaptadas, as técnicas foram aplicadas a amostras de urinas de trabalhadores expostos a compostos de urânio ou trítio com a finalidade de verificar possível contaminação interna por estes radioisótopos. / Abstract not available.

A cotinina, principal produto de biotransformação da nicotina, é considerada um excelente marcador biológico de exposição tanto para fumantes ativos quanto passivos. A cotinina apresenta maior estabilidade química que a nicotina e possui uma meia vida de eliminação de cerca de 40 horas. Assim, um método analítico sensível, preciso e exato foi desenvolvido, para sua determinação, empregando-se a cromatografia em fase gasosa com coluna capilar (HP-Ultra2, 25m x 0.20mm x 0.33µm) e detetor de nitrogênio e fósforo (CGIDNP). A nicotina e a cotinina foram extraídas sob condições alcalinas com diclorometano, de amostras de urina às quais foi adicionado o padrão interno (clorprenalina). Após evaporação do extrato sob fluxo de nitrogênio, o resíduo foi retomado utilizando-se 50 µL de metanol onde 1 µL foi injetado no CG/DNP. O método mostrou-se linear na faixa de 10 a 200 ng/mL com coeficiente de correlação (r) igual a 0,0965 e 0,9966 para a cotinina e nicotina, respectivamente. Os limites de detecção e quantificação foram 5 ng/mL e 10 ng/mL, tanto para a cotinina quanto para a nicotina. A nicotina e a cotinina mantiveram-se estável por 15 e 21 dias a 20°C. A avaliação das amostras de urina de algumas crianças evidenciaram o contato com pais ou parentes fumantes, apresentando resultados de cotinina entre 13,70 a 272,60 ng/mL. O método validado neste trabalho mostrou-se apropriado para a avaliação da presença de cotinina em amostras de urina de fumantes passivos, apresentando as vantagens de fácil execução, curto tempo de análise e baixo custo. / Cotinine, the principal product of biotransformation of nicotine, is considered an excellent biological marker to measure the exposure to cigarette smoke for both the active and passive smokers. Cotinine presents a higher chemical stability than the nicotine and it possesses a half-life of elimination of approximate 40 hours. Therefore, a sensible analytical method, very precise and accurate, was developed using a process of gas chromatography with a nitrogen phosphorous detector (GC/NPD). Nicotine and the cotinine were extracted, under alkaline conditions with dichloromethane, from urine samples which had the internal standard clorprenaline added to them. After evaporation of the extract under nitrogen flux, the residue was retaken using 50 µL of methanol, where 1 µL was injected in the GC/NPD. The method proved to be linear in the range of 10 to 200 ng/mL with a coefficient of correlation (r) equal to 0,0965 and 0,9966 to cotinine and nicotine, respectively. The limits of detection and quantification were 5ng/mL and 10ng/mL for both cotinine and nicotine. Nicotine and cotinine maintained themselves stable for 15 and 21 days at -20 C°. The evaluation of same urine samples taken fron children passively exposured to tobacco throgh there parentes or relatives evidenced cotinine levels fron 13,70 to 272,60 ng/mL. The validated method in this work proved to be appropriate for the evaluation of the cotinine presence in the urine samples taken from.

M.Sc. / The upper catchment of the Olifants River, from its origin near Bethal, to its confluence with the Wilge River, north of Witbank, as well as it tributaries, are being subjected to increasing afforestation, mining, power generation, irrigation, domestic and industrial activities. These activities have a profound effect on the water quality and the major point sources of pollution in this area include mines, industries and very importantly, combined sewage purification works, located alongside the river, which, in addition to oxidizable material contains detergents, nutrients, and metals. It was therefore necessary to determine the extent to which these activities affect the water quality of the system. The impact of these activities was therefore addressed by a Water Research Commision Project namely "Lethal and sublethal effects of metals on the physiology of fish" of which the present study investigated effects at two localities, namely in the Olifants River (locality OR1) before its confluence with the Klein Olifants River and a locality in the Klein Olifants River (locality KOR1). Apart from the field study, toxicity tests were also performed in a laboratory, in order to determine the effects of low pH and elevated aluminium concentrations on the haematology, osmoregulation and carbohydrate metabolism of the Mozambique Tilapia, Oreochromis mossambicus as the acidification of soil systems may cause the transfer of aluminium into aqueous solutions, where it may be present in different forms. During the field study, the chemical and physical characteristics of the river water were evaluated, with special attention to the concentrations of certain metals (manganese, copper, chromium, lead, nickel, zinc, iron and aluminium) in the water and sediment, as well as in fish, which are known to accumulate the elements supra and are therefore valuable as indicators of these pollutants. The two fish species used for the investigations were the African sharptooth catfish, Clarias gariepinus and the moggel, Labeo umbratus. Four tissue types were dissected, namely the muscle, liver, skin and gill tissues. The metal concentrations in these organs/tissues, as well as in the water and sediment, were determined in a laboratory with an atomic absorption spectrophotometer. Statistical analyses were performed on the results obtained from this study and the order and extent of bioaccumulation of these metals in the water and sediment were determined, as well as in the fish organs/tissues. Its dependence on the size, sex and species of the fish and the localities and seasons were investigated.

As microcistinas constituem uma família de heptapeptídeos cíclicos com cerca de 70 variantes caracterizadas. São biossintetizadas em condições específicas por cianobactérias, principalmente em corpos d\'água eutrofizados. Apresentam organotropismo ao fígado e DL50 entre 50-500 µg.kg-1 peso (rato, i.p.). A exposição aguda pode impactar a saúde humana ao desarranjar o parênquima hepatocelular por hiperfosforilação do citoesqueleto e produzir intenso sangramento, podendo levar à morte por choque hipovulêmico um homem adulto e são promotoras tumorais, quando ocorre exposição crônica, por inibição de fosfatases 1 e 2A. Os congêneres das microcistinas apresentam toxicidades distintas e é importante caracterizá-los em corpos d\'água para se estimar o risco à saúde humana. Na literatura, não há convergência quanto à forma de extração das toxinas, preparo das amostras para análise e condições cromatográficas para o isolamento e quantificação. Neste trabalho, diversas análises foram conduzidas para se determinar as melhores formas de extração das toxinas, clean up da amostra e condições cromatográficas para amostras de campo ou cultura de cianobactérias. A extração hidro-alcoólica (MeOH:H2O, 3:1, v/v) parece ser a melhor forma de extração, seguida de partição líquido-líquido para amostras de campo (florações) e extração em fase sólida (cartuchos C18) para algas cultivadas em laboratório. Por meio de isolamento por cromatografia líquida de alta eficiência (HPLC) com detectores UV-VIS e pela análise do padrão de fragmentação das moléculas por espectrometria de massas (MS) com ionização por eletrospray em Tandem (ESI-MS/MS) determinou-se a presença das variantes de microcistinas MC-RR, MC-LR, MC-YR e MC-hRhR na amostra de água do Reservatório Billings e [Asp3]MC-LR na cepa Microcystis aeruginosa BCCUSP 235. Este método parece ser adequado para a extração e caracterização de microcistinas presente em corpos d\'água e em cultura de laboratório e a variante MC-hRhR foi caracterizada pela primeira vez na literatura mundial. / It is well known that eutrophicated lakes and water reservoirs can be a serious concern to wildlife, domestic livestock and human health since cyanobacterial blooms are prone to occur. Some cyanobacteria (blue-green algae) species which form bloom may biosynthesize a family of hepatotoxic peptides named microcystins under certain circumstances, related specially to nitrogen: phosphorus ratio, temperature, pH and light intensity of the water body. There are at least 70 variants of microcystins with different toxicity, DL50 ranging from 50 to 500 µg.kg-1 (in mouse, i.p.). Acute exposure provoke hyperphosphorylation of the cytoskeleton, in liver cells, leading to cellular disruption with haemorrhage and the long term exposure can cause tumor promotion by inactivation of serine/threonine phosphatases 1 and 2A (PP1 and PP2A). Therefore, it is very important to determine and quantify microcystin variants present in water reservoirs. There are several methods available to evaluate qualitative and quantitatively microcystin and its variants in water reservoir and estimate human risks. Such methods comprise biological, biochemical and physico-chemical assays. In this work, we have isolated and analyzed hepatotoxins by High Performance Liquid Chromatography (HPLC) with photodiode array (PDA) detector and their structures were elucidated by Tandem - MS/MS with eletrospray ionization (ESI-MS/MS). MC-RR, MC-LR, MC-YR and MC-hRhR were determined in samples collected at Billings reservoir and [Asp3]MC-LR was found in the strain Microcystis aeruginosa BCCUSP 235. The procedures developed herein can be a powerful tool for isolation and determination of microcistin and its derivatives founded in water reservoirs. Also, we have described for the first time a new variant of microcistin: MC-hRhR.

Masters of Science / It is well documented that cigarette smoking and nicotine exposure create widespread physiological disorders in humans and animals. The primary tobacco constituent that is responsible for the toxicological consequences associated with the effects of tobacco smoke is nicotine (Van Lancker 1977). After maternal nicotine exposure, the fetal gonads and lungs are the principle sites of nicotine damage (Szuts et al. 1978, Mosier & Jansons 1972). Whilst the fetal lung has received widespread attention in this regard (Maritz 1988), the testis has never been studied. Therefore, I have chosen to explore the effects of maternal nicotine exposure on the testis of male offspring by evaluating various aspects of the male reproductive tract. It is believed that, in adult male smokers (Rosenberg 1987, Handelsman et al. 1984) and sexually mature animals (Mattison 1982) that are exposed to nicotine, male fertility may be compromised. However, these studies provide conflicting data on single parameters. It was therefore my objective to identify the effect of nicotine exposure on the male reproductive tract and to establish possible sites through which these effects may be mediated in adult male rats. The influence of nicotine was then investigated in male offspring after maternal nicotine treatment (MNT), and in sexually mature adult males after direct adult nicotine treatment (ANT). In the former experiment (MNT), 7 day pregnant rats were exposed to Img nicotine/kg body weight/day. Therefore, these offspring were indirectly exposed to nicotine during fetal development and early neonatal development. After weaning the animals were divided into two groups. One group did not receive further treatment (withdrawn group), whilst the other group was continually treated till adulthood (nicotine group), after which both groups were sampled together with the control. In the latter experiment (ANT), the animals were treated daily for 3 weeks and were sampled as above (MNT animals). The fundamental parameter investigated in both experiments to assess reproductive status was sperm quality (motility and morphology). Thereafter, it was necessary to establish a possible site where the effects of nicotine would occur. Testicular growth, epididymal structure, and plasma testosterone content were measured as probable localities of nicotine's effect. The results signify that maternal nicotine exposure poses a greater threat to the male reproductive system than adult nicotine exposure. In the MNT experiment, progressive sperm motility of the nicotine and withdrawn groups were 1.7% and 3.4% respectively. The proportion of abnormal sperm was 72% in each of the above groups. The lower quality sperm that is evident after nicotine exposure implies that the fertilizing ability of the animals may be impaired during adulthood. The data on testicular growth indicates that nicotine exposure during early development results in slower testicular development until maturity. The epididymal lining of these animals also increased after nicotine exposure, indicating increased cellular activity. However, these results from testicular and epididymal studies are inconclusive and need further work. In the ANT experiment, progressive sperm motility of the nicotine group was 1.2%, whilst the proportion of abnormal sperm was 58%. No other parameter was affected after nicotine exposure to adult animals. From the above data it is evident that nicotine exposed animals were subject to greater nicotine damage after maternal nicotine exposure during early development. Moreover, within the maternal nicotine treated experiment, the withdrawal of nicotine after weaning did not appear to reverse the injurious effects of nicotine that were established during early development. These effects were evident since the nicotine and withdrawn groups showed similar levels of damage in all instances. The most profound effects after adult nicotine exposure and maternal nicotine exposure were on sperm quality. The probable site of sperm impairment appears to be via retarded testicular growth and possibly, structural status of the epididymis after maternal nicotine exposure. The results from adult nicotine exposure however, suggest that sperm cells may be directly affected by nicotine exposure. An epidemiological survey was included to validate the basic conclusions established in animal research when compared to clinical data from human patients. No statistically significant changes were observed in this study between the patient's spermiogram results versus his smoking habits, and, that of his mother. From the level of significance it was concluded that cigarette smoking does not appear to be a cause of impaired fertility in already infertile patients. However, the data does suggest that cigarette smoking may well be a precipitating agent in male infertility. Experimentally, nicotine exposure impairs the male reproductive system to some extent. The effects of which are irreversible after indirect exposure (MNT) during development and may begin with poor testicular development. The effects of adult nicotine exposure implies that nicotine exposure in mature animals (ANT) acts directly on sperm cells to incapacitate them. It is well advised that cigarette smoking should be curbed in pregnant women and in adult males to alleviate contributing effects to male infertility.

Development and validation of methods for analysis of several drugs or their metabolites are decribed in this thesis. The document is presented as a commentary to the original papers, which were published in peer reviewed journals. Discussion on the optimization of each method is presented and covers also method development and influence of preanalytical aspects. Additionally, examples of the application of the developed methods in clinical pharmacology and toxicology are shown. This dissertation consists of three parts: enantiomeric determination of tramadol and its metabolite, determination of some antihypertensive drugs, and qualitative analysis of benzodiazepines. Development of a method for chiral analysis of tramadol and its desmethylated metabolite O- desmethyltramadol (ODT) in human urine and plasma is described in the first part of the thesis. Tramadol is a centrally acting analgetic drug, which is used as racemate in clinical practise. Each enantiomer displays different binding properties for various receptors: (+)-tramadol preferentially inhibits serotonin reuptake while (-)-tramadol mainly inhibits noradrenalin reuptake. (+)-tramadol is considered 10-times more potent than (-)-tramadol. Major active metabolite (ODT), which is considered to be the main agent responsible for the...

The distribution, absorption, metabolism and tissue binding of radioactivity were studied in hamsters after oral and intraperitoneal administration of alpha-chaconine- (3H). The material was well absorbed from the gastrointestinal tract and nearly 22 percent of the label was excreted via urine and feces in 7 days. The excretion was higher in urine (21 percent) than in feces ( < 1 percent). Tissue concentrations of radioactivity peaked at 12 hours following oral administration, with the highest concentrations found in lungs, liver, spleen, skeletal muscle, kidney and pancreas, with heart and brain containing moderate amounts. Concentrations of radioactivity in tissues following intraperitoneal administration were significantly higher than those observed after oral treatment. Excretion of chloroform-soluble products in the feces was 10 times higher than that of the chloroform-insoluble metabolites after both oral and intraperitoneal administration. In the urine, the activity was predominantly in the chloroform-insoluble form and the chloroform-soluble metabolites were relatively minor in amounts (0.27, 0.85, and 2.45 percent versus 0.005, 0.14 and 0.19 percent of dose for 12, 24 and 72 hours, respectively). After 7 days, the chloroform-soluble metabolites in urine increased to 20 percent of the excreted radioactivity, while the amount of chloroform-insoluble metabolites was less than 1 percent. Subcellular distribution of the labeled compound indicated the highest concentration of radioactivity in the nuclear and microsomal fractions of brain, liver and heart tissues. A small amount of radioactivity, shown by a minor peak, was also observed in the fractions between the mitochondrial and microsomal fractions on a sucrose gradient. Binding of radioactivity was observed in brain, testes, kidney, lung, liver and heart . All of the label in the brain appeared to be in the bound form . The results indicated that alpha-chaconine is slowly absorbed from the gastrointestinal tract after oral administration, and persists in various tissues, much of it in bound (non-extractable) form (in nuclear and microsomal fractions). Excretion of alpha-chaconine- (3H) and its metabolites was investigated after oral and intraperitoneal administration in hamsters. The separation of the glycoalkaloid and its metabolites in feces and urine was accomplished by thin-layer chromatography. An increase in the concentration of excreted alpha-chaconine metabolites in feces and urine was observed. In urine over 50 percent of the eliminated radioactivity during the initial 24 hours was due to the aglycone, solanidine. The fraction of the total dose administered which was excreted represented only 27 percent (26 percent in feces and less than 1 percent in urine) during the 7 day test period. Contrary to the general belief that potato glycoalkaloid absorption is poor following oral administration, only 5 percent or less was excreted in feces during the initial 72 hours, a fact explained by the binding of radioactivity to tissues. Inhibition of acetylcholinesterases by alpha-chaconine was studied. The inhibition of purified erythrocyte acetylcholinesterase and horse serum cholinesterase by alpha-chaconine was found to be a mixed-type with kinetic constants. An inhibition constant (Ki) for both the specific and pseudocholinesterases was 8.3 x 10-6 M and 4.0 x 10-4 M, respectively. Kinetic constants obtained for both enzymes were as follows: Vmax of 7.14 x 10-5 and 3.76 x 10-4 max moles/liter/min, respectively, and Km of 6.2 x 10-5 and 1.33 x 10-4, respectively. The distribution of acetylcholinesterase among the subcellular fractions of rat brain homogenate separated by sucrose density gradient centrifugation was determined, as well as the inhibition pattern of these fractions following in vitro incubation with 0.016 M alpha-chaconine. Enzyme activity was found to be distributed equally between the mitochondrial and microsomal fractions, with the nuclear fraction having the least activity. Percentage inhibition of the various fractions obtained was: whole homogenate 43, nuclear fraction 55, mitochondria 35, and microsomes 33. Brain acetyl cholinesterase activity of animals given intraperitoneal doses (10, 30, 60 mg / Kg) of alpha-chaconine was 79, 55 and 18 percent of the control group. Acetylcholinesterase activity of heart and plasma of animals administered alpha-chaconine did not show the dose-related response observed in the brain. Inhibition of heart acetylcholinesterase was 61 percent, while plasma gave 51 percent for the rats given a dose of 10 mg/Kg and no inhibition for rats given 30 mg/ Kg. Acrylamide gel electrophoretic separation of cholinesterases in aqueous homogenates from whole brain and heart of adult male rats administered alpha-chaconine was investigated. Brain acetylcholinesterase isoenzymes were found to be inhibited by 30 and 60 mg/ Kg dosage levels of alpha-chaconine administered intraperitoneally. Electrophoretic separation of plasma from the treated animals resulted in five anodally migrating zones having properties of cholinesterases. These sites hydrolyze acetylthiocholine and alpha-naphthylacetate, and all were inhibited by alpha-chaconine except the slowest migrating band (band 5). Inhibition of isoenzyme activity of bands 1 and 2 is observed for the groups administered 10 and 30 mg/Kg alpha-chaconine with the percentage inhibition of both bands (l and 2) being 40 and 77 percent for animals given 10 mg/Kg and 100 and 75 percent for the latter group. Isoenzyme bands 3 and 4 were completely absent in the alkaloid treated animals. Inhibition of non-specific cholinesterase isoenzymes (butyrylthiocholine hydrolyzable bands) by alpha-chaconine was clearly demonstrated. In vitro inhibition of plasma, erythrocyte and brain esterase isoenzymes was estimated by incubating gels with 10-4 M alpha-chaconine after the electrophoretic separations. With this concentration of alpha-chaconine, the various isoenzymes in rat plasma, erythrocyte and brain showed some response to the inhibitory potency of alpha-chaconine. The slower-moving isoenzyme bands were inhibited to 100 percent with the different concentrations of inhibitor. The fast migrating isoenzyme bands in plasma and erythrocytes were least affected by alpha-chaconine (10-4 M), with no inhibition. Plasma protein isoenzymes from adult male rats were not affected by alphachaconine.

X-ray flourescence (XRF) and atomic absorption spectrophotometry (AAS) measurements for manganese, iron, copper, and zinc were compared for 96 samples of 21 foods from different sources. Correlation coefficients were 0.94 for manganese, 0.99 for iron, 0.93 for copper, and 0.91 for zinc for XRF vs. AAS determinations. Similiar comparisons were performed on 228 samples of fast foods purchased in Utah retail outlets. Correlation coefficients ranged from 0.91 for copper to 0.97 for iron and zinc. Comparisons of values generated by XRF for manganese, iron, copper, zinc, selenium, arsenic, and aluminum to values certified by the National Bureau of Standards indicated no significant differences by student's t tests. The simultaneous multielement capabilities of XRF allowed for an extensive screening study for high levels of toxic minerals in the fast foods. Levels of selenium, arsenic, and aluminum in fast foods were determined by XRF. Inductively coupled plasma was used to screen for high cadmium levels since cadmium detection limits by XRF were too high to be of value.

This study was designed to accomplish two primary objectives: (1) to compare two test methods commonly used to evaluate toxicity of inhaled air pollutants, and (2) to observe the response as measured by each of the methods, of pulmonary alveolar macrophages exposed to 2μg hexavalent chromium. The firs t method evaluated featured use of intratracheal injections to simulate live inhalation exposures, and the second required exposure of macrophages cultured on petri plates. Pulmonary alveolar macrophages harvested from Long Evans rats were used. The two cell function parameters measured in the evaluations were chemiluminescence and oxygen consumption (which was determined for cells at rest and during phagocytosis). These two tests have been shown to be sensitive indicators of macrophage damage. Results of CL output and oxygen consumption revealed the two methods were significantly different. Evaluation of macrophages from live animals treated with CrO3 or CaCrO4showed no differences between their respective untreated controls as determined by measurement of their chemiluminescence production or of oxygen consumption rates. Alveolar macrophages that were cultured in media during treatment with the same two forms of hexavalent chromium showed statistically significant differences from untreated controls. These comparisons indicate that choices of investigative toxicological models influence interpretation of data recorded.