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Int. J. Environ. Res. Public Health, Volume 3, Issue 2 (June 2006), Pages 121-216

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Research

Open AccessArticle The L1 Retrotranspositional Stimulation by Particulate and Soluble Cadmium Exposure is Independent of the Generation of DNA Breaks
Int. J. Environ. Res. Public Health 2006, 3(2), 121-128; doi:10.3390/ijerph2006030015
Received: 5 October 2005 / Accepted: 2 June 2006 / Published: 30 June 2006
Cited by 6 | PDF Full-text (197 KB) | HTML Full-text | XML Full-text
Abstract
Human exposure to toxic metals is a concern of the highest priority, due to their vast array of biological effects, including carcinogenicity. The particulate (water insoluble) form of several heavy metals presents a higher carcinogenic potential than its soluble counterparts. Our previous work
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Human exposure to toxic metals is a concern of the highest priority, due to their vast array of biological effects, including carcinogenicity. The particulate (water insoluble) form of several heavy metals presents a higher carcinogenic potential than its soluble counterparts. Our previous work demonstrates that the particulate forms of different heavy metals, such as nickel oxide, cadmium sulfide and mercury sulfide, stimulate human L1 mobile element activity leading to genomic instability. We present data demonstrating that the soluble form of CdCl2 also stimulates L1 retrotransposition in a dose-dependent manner comparable to the insoluble carcinogenic form of this compound. Reproducible results demonstrated a 2 to 3 fold dose-dependent increase in L1 retrotransposition compared to control cells. Heavy metals may cause DNA breaks through the generation of reactive oxygen species. However, evaluation of DNA damage by comet assay revealed no differences between the negative controls and the CdS-treated cells. In addition, active L1 elements express a protein with endonuclease activity that can generate toxicity through the creation of double strand breaks. To determine the contribution of the L1 endonuclease to the toxicity observed in our metal treatment assays, we compared the wildtype L1 vector with an L1 endonuclease-mutant vector. The presence of an active L1 endonuclease did not contribute significantly to the toxicity observed in any of the CdCl2 or CdS doses evaluated. No correlation between the creation of DNA breaks and L1 activity was observed. Alternatively, heavy metals inhibit enzymatic reactions by displacement of cofactors such as Zn and Mg from enzymes. Concomitant treatment with Mg(Ac)2 and Zn(Ac)2 ppb suppresses the stimulatory effect on L1 activity induced by the 3.8 ppb CdS treatment. Overall, these results are consistent with our previous observations, suggesting that the mechanism of L1 stimulation by heavy metals is most likely due to an overall inhibition of DNA repair proteins or other enzymes caused by the displacement of Mg and Zn from cellular proteins. Full article
Open AccessArticle The Evolution of Depleted Uranium as an Environmental Risk Factor: Lessons from Other Metals
Int. J. Environ. Res. Public Health 2006, 3(2), 129-135; doi:10.3390/ijerph2006030016
Received: 4 November 2005 / Accepted: 31 May 2006 / Published: 30 June 2006
Cited by 20 | PDF Full-text (165 KB) | HTML Full-text | XML Full-text
Abstract
Depleted uranium (DU) is used in both civilian and military applications. Civilian uses are primarily limited to ballast and counterweights in ships and aircraft with limited risk of environmental release. The very nature of the military use of DU releases DU into the
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Depleted uranium (DU) is used in both civilian and military applications. Civilian uses are primarily limited to ballast and counterweights in ships and aircraft with limited risk of environmental release. The very nature of the military use of DU releases DU into the environment. DU released into the environment from military use takes the form of large fragments that are chemically unchanged and dust in the form of oxides. DU dust is nearly insoluble, respirable and shows little mobility in the soil. Exposure to DU occurs primarily from inhalation of dust and possible hand to mouth activity. Toxicity of DU is believed to be primarily chemical in nature with radiological activity being a lesser problem. DU has been shown to have a variety of behavioral and neurological effects in experimental animals. DU has been used the Balkans, Afghanistan, and both Iraq wars and there is a high probability of its use in future conflicts. Further, other nations are developing DU weaponry; some of these nations may use DU with a greater radiological risk than those currently in use. The toxicity of DU has been studied mostly as an issue of the health of military personnel. However, many tons of DU have been left in the former theater of war and indigenous populations continue to be exposed to DU, primarily in the form of dust. Little epidemiological data exists concerning the impact of DU on these groups. It may be possible to extrapolate what the effects of DU may be on indigenous groups by examining the data on similar metals. DU has many similarities to lead in its route of exposure, chemistry, metabolic fate, target organs, and effect of experimental animals. Studies should be conducted on indigenous groups using lead as a model when ascertaining if DU has an adverse effect. Full article
Open AccessArticle Dose- and Time-Dependent Response of Human Leukemia (HL-60) Cells to Arsenic Trioxide Treatment
Int. J. Environ. Res. Public Health 2006, 3(2), 136-140; doi:10.3390/ijerph2006030017
Received: 15 January 2006 / Accepted: 12 April 2006 / Published: 30 June 2006
Cited by 27 | PDF Full-text (154 KB) | HTML Full-text | XML Full-text
Abstract
The treatment of acute promyelocytic leukemia (APL) has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional
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The treatment of acute promyelocytic leukemia (APL) has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60) cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60) cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia. Full article
Open AccessArticle Microarray Analysis of Mercury-Induced Changes in Gene Expression in Human Liver Carcinoma (HepG2) Cells: Importance in Immune Responses
Int. J. Environ. Res. Public Health 2006, 3(2), 141-173; doi:10.3390/ijerph2006030018
Received: 28 October 2005 / Accepted: 5 June 2006 / Published: 30 June 2006
Cited by 17 | PDF Full-text (969 KB) | HTML Full-text | XML Full-text
Abstract
Mercury is widely distributed in the biosphere, and its toxic effects have been associated with human death and several ailments that include cardiovascular diseases, anemia, kidney and liver damage, developmental abnormalities, neurobehavioral disorders, autoimmune diseases, and cancers in experimental animals. At the cellular
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Mercury is widely distributed in the biosphere, and its toxic effects have been associated with human death and several ailments that include cardiovascular diseases, anemia, kidney and liver damage, developmental abnormalities, neurobehavioral disorders, autoimmune diseases, and cancers in experimental animals. At the cellular level, mercury has been shown to interact with sulphydryl groups of proteins and enzymes, to damage DNA, and to modulate cell cycle progression and/or apoptosis. However, the underlying molecular mechanisms of mercury toxicity remain to be elucidated. Our laboratory has demonstrated that mercury exposure induces cytotoxicity and apoptosis, modulates cell cycle, and transcriptionally activates specific stress genes in human liver carcinoma cells. The liver is one of the few organs capable of regeneration from injury. Dormant genes in the liver are therefore capable of reactivation. In this research, we hypothesize that mercury-induced hepatotoxicity is associated with the modulation of specific gene expressions in liver cells that can lead to several disease states involving immune system dysfunctions. In testing this hypothesis, we used an Affymetrix oligonucleotide microarray with probe sets complementary to more than 20,000 genes to determine whether patterns of gene expressions differ between controls and mercury (1-3μg/mL) treated cells. There was a clear separation in gene expression profiles between controls and mercury-treated cells. Hierarchical cluster analysis identified 2,211 target genes that were affected. One hundred and thirty-eight of these genes were up-regulated, among which forty three were significantly over-expressed (p = 0.001) with greater than a two-fold change, and ninety five genes were moderately over-expressed with an increase of more than one fold (p = 0.004). Two thousand and twentythree genes were down-regulated with only forty five of them reaching a statistically significant decline at p = 0.05 according to the Welch’s ANOVA/Welch’s t-test. Further analyses of affected genes identified genes located on all human chromosomes except chromosome 22 with higher than normal effects on genes found on chromosomes 1-14, 17-20 (sex-determining region Y)-box18SRY, 21 (splicing factor, arginine/serine-rich 15 and ATP-binding), and X (including BCL6-co-repressor). These genes are categorized as control and regulatory genes for metabolic pathways involving the cell cycle (cyclin-dependent kinases), apoptosis, cytokine expression, Na+/K+ ATPase, stress responses, G-protein signal transduction, transcription factors, DNA repair as well as metal-regulatory transcription factor 1, MTF1 HGNC, chondroitin sulfate proteoglycan 5 (neuroglycan C), ATPbinding cassette, sub-family G (WHITE), cytochrome b-561 family protein, CDC-like kinase 1 (CLK1 HGNC) (protein tyrosine kinase STY), Na+/H+ exchanger regulatory factor (NHERF HGNC), potassium voltage-gated channel subfamily H member 2 (KCNH2), putative MAPK activating protein (PM20, PM21), ras homolog gene family, polymerase (DNA directed), δ regulatory subunit (50kDa), leptin receptor involved in hematopoietin/interferon-class (D200-domain) cytokine receptor activity and thymidine kinase 2, mitochondrial TK2 HGNC and related genes. Significant alterations in these specific genes provide new directions for deeper mechanistic investigations that would lead to a better understanding of the molecular basis of mercury-induced toxicity and human diseases that may result from disturbances in the immune system. Full article
Open AccessArticle Aqueous Vernomia amygdalina Extracts Alter MCF-7 Cell Membrane Permeability and Efflux
Int. J. Environ. Res. Public Health 2006, 3(2), 174-179; doi:10.3390/ijerph2006030019
Received: 10 November 2005 / Accepted: 6 June 2006 / Published: 30 June 2006
Cited by 13 | PDF Full-text (171 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer is the second leading cause of cancer related deaths of women in the United States. Several treatment strategies have been developed over the past decade to reduce cancer morbidity and mortality rates. While mortality rates have declined in some ethnic populations,
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Breast cancer is the second leading cause of cancer related deaths of women in the United States. Several treatment strategies have been developed over the past decade to reduce cancer morbidity and mortality rates. While mortality rates have declined in some ethnic populations, the overall cancer incidence continues to grow. Hence, chemotherapeutic agents are needed to improve cancer treatment outcome. Previous studies show that low concentrations (microgram/ml) of water-soluble leaf extracts of a Nigerian edible plant, V. amygdalina (VA), potently retard the proliferative activities of estrogen receptor positive (ER+) human breast cancerous cells (MCF-7) cells in vitro in a concentration-dependent fashion. The anti-proliferative activities of VA are extracellular signal-regulated kinases 1/2 (ERKs 1/2)-dependent. Cell culture and animal model studies, conducted by other investigators using other plant extracts, have also revealed that plant extract components called thionins may be responsible for their anticancer activities. These thionins are believed to interact with the cells in ways that compromise membrane potential/permeability resulting in the alteration of efflux, cytosolic activities, and subsequent cell death. Therefore, we hypothesized that VA exposure may compromise cell membrane as another mode of action to elicit its anticancer activities in MCF-7 cells. The exposure of cells to VA decreased [3H]thymidine uptake in a concentration-dependent (0, 30, and 100 μg/ml VA) manner (p < 0.05) but increased [3H]thymidine release, expressed as percent of [3H]thymidine incorporated, into the medium (p < 0.05). The amount of [3H]thymidine released into the medium was 1.7, 7.4, and 11.0 % for 0, 30, and 100 μg/ml VA respectively. Thus suggesting the membranes in VA-treated cells were compromised in a concentration-dependent fashion. Full article
Open AccessArticle Are Endocrine Disrupting Compounds a Health Risk in Drinking Water?
Int. J. Environ. Res. Public Health 2006, 3(2), 180-184; doi:10.3390/ijerph2006030020
Received: 31 August 2005 / Accepted: 31 May 2006 / Published: 30 June 2006
Cited by 29 | PDF Full-text (130 KB) | HTML Full-text | XML Full-text
Abstract
There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North
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There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17β-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where he effluent is directly or indirectly in use for drinking water. In some places at which heavy anthropogenic contamination of drinking water sources occurs, advanced drinking water treatment is increasingly being implemented. This treatment employs particle removal, ozone oxidation of organic material and activated charcoal adsorption of the oxidation products. Such processes will remove industrial organic chemicals, pesticides, detergents, pharmaceutical products and hormones. Populations for which only basic wastewater and drinking water treatment are available remain vulnerable. Full article
Open AccessArticle Photoirradiation of Retinyl Palmitate in Ethanol with Ultraviolet Light - Formation of Photodecomposition Products, Reactive Oxygen Species, and Lipid Peroxides
Int. J. Environ. Res. Public Health 2006, 3(2), 185-190; doi:10.3390/ijerph2006030021
Received: 16 February 2006 / Accepted: 5 June 2006 / Published: 30 June 2006
Cited by 19 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
We have previously reported that photoirradiation of retinyl palmitate (RP), a storage and ester form of vitamin A (retinol), with UVA light resulted in the formation of photodecomposition products, generation of reactive oxygen species, and induction of lipid peroxidation. In this paper, we
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We have previously reported that photoirradiation of retinyl palmitate (RP), a storage and ester form of vitamin A (retinol), with UVA light resulted in the formation of photodecomposition products, generation of reactive oxygen species, and induction of lipid peroxidation. In this paper, we report our results following the photoirradiation of RP in ethanol by an UV lamp with approximately equal UVA and UVB light. The photodecomposition products were separated by reversed-phase HPLC and characterized spectroscopically by comparison with authentic standards. The identified products include: 4-keto-RP, 11-ethoxy-12-hydroxy-RP, 13-ethoxy-14-hydroxy-RP, anhydroretinol (AR), and trans- and cis-15-ethoxy-AR. Photoirradiation of RP in the presence of a lipid, methyl linoleate, resulted in induction of lipid peroxidation. Lipid peroxidation was inhibited when sodium azide was present during photoirradiation which suggests free radicals were formed. Our results demonstrate that, similar to irradiation with UVA light, RP can act as a photosensitizer leading to free radical formation and induction of lipid peroxidation following irradiation with UVB light. Full article
Open AccessArticle UVA Photoirradiation of Halogenated-Polycyclic Aromatic Hydrocarbons Leading to Induction of Lipid Peroxidation
Int. J. Environ. Res. Public Health 2006, 3(2), 191-195; doi:10.3390/ijerph2006030022
Received: 13 August 2005 / Accepted: 5 June 2006 / Published: 30 June 2006
Cited by 12 | PDF Full-text (167 KB) | HTML Full-text | XML Full-text
Abstract
Since the finding in the 1930s, a large number of polycyclic aromatic hydrocarbons (PAHs) of different structures have been tested for potential tumorigenicity. Structure-activity relationships of halo-PAHs have been investigated to determine the regions of a PAH that may be involved in cancer
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Since the finding in the 1930s, a large number of polycyclic aromatic hydrocarbons (PAHs) of different structures have been tested for potential tumorigenicity. Structure-activity relationships of halo-PAHs have been investigated to determine the regions of a PAH that may be involved in cancer initiation. From these studies, a number of halo-PAHs were found to be tumorigenic in experimental animals. It was not until the 1980s that halo-PAHs were found to be present in the environment, including municipal incinerator fly ash, urban air, coal combustion, soil, snow, automobile exhausts, and tap water. Due to their widespread presence in the environment and their genotoxic activities, including carcinogenicity, many of these compounds may pose a health risk to humans. Although the biological activities, including metabolism, mutagenicity, and carcinogenicity, of halo-PAHs have been studied their phototoxicity and photo-induced biological activity have not been well examined. In this study, we study the photoirradiation of a series of structure-related halo-PAHs by UVA light in the presence of a lipid, methyl linoleate, and determine as to whether or not these compounds can induce lipid peroxidation. The halo-PAHs chosen for study include 2-bromonaphthalene, 1-chloroanthracene, 9,10-dibromoanthracene, 9-chlorophenanthrene, 9-bromophenanthrene, 7-chlorobenz[a]anthracene, 7-bromobenz[a]anthracene, 7-bromo-5-methylbenz[a]anthracene, 6-chlorobenzo[a]pyrene, and 6-bromobenzo[a]pyrene. The results indicate that upon photoirradiation by UVA all these compounds induced lipid peroxidation at different levels. These results suggest that halo-PAHs may be harmful to human health. Full article
Open AccessArticle Toxic Elements in Soil and Groundwater: Short-Time Study on Electrokinetic Removal of Arsenic in the Presence of other Ions
Int. J. Environ. Res. Public Health 2006, 3(2), 196-201; doi:10.3390/ijerph2006030023
Received: 6 February 2006 / Accepted: 31 May 2006 / Published: 30 June 2006
Cited by 2 | PDF Full-text (158 KB) | HTML Full-text | XML Full-text
Abstract
The electrokinetic technique is an emerging technology presently tested in situ to remove dissolved heavy metals from contaminated groundwater. There is a growing interest for using this system to cleanse clayey soil contaminated by toxic metallic ions. Currently, there are very few available
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The electrokinetic technique is an emerging technology presently tested in situ to remove dissolved heavy metals from contaminated groundwater. There is a growing interest for using this system to cleanse clayey soil contaminated by toxic metallic ions. Currently, there are very few available non-destructive treatment methods that could be successfully applied in situ on low permeable type of soil matrix. The main objective of presented study was to validate and possibly enhance the overall efficiency of decontamination by the electrokinetic technique of the low permeable soil polluted by the arsenic in combination with chromium and copper ions. The chosen mixture of ions was imitating leak of pesticide well known as chromate copper arsenate (CCA). The chosen technique is showing a big promise to be used in the future as a portable, easy to install and run on sites with spills or leaks hard to reach otherwise; such as in the dense populated and urbanized areas. Laboratory electrokinetic experiments were designed to understand and possibly manipulate main mechanisms involved during forced migration of ions. All tests were conducted on artificially contaminated kaolinite (low permeable clay soil). Electrokinetic migration was inducted by the low voltage dc current applied through soil column. Series of experiments were designed to assess the efficiency of arsenic-chromium-copper remediation by applying (1) only dc current; and (2) by altering the soil environment. Obtained results showed that arsenic could be successfully removed from the soil in one day (25 hours) span. It was significant time reduction, very important during emergency response. Mass recovered at the end of each test depended on initial condition of soil and type of flushing solution. The best results were obtained, when soil was flushed with either NaOH or NaOCl (total removal efficiency 74.4% and 78.1%, respectively). Direct analysis of remained arsenic in soil after these tests confirmed substantial drop of the initial mass of arsenic in soil profile from 51.54 mg to 10.62 mg (NaOH) and 5.68 mg (NaOCl) after 25 hours of treatment. Full article
Open AccessArticle Molecular Modeling Studies of the Binding Characteristics of Phosphates to Sevelamer Hydrochloride – Assessing a Novel Technique to Reduce Phosphates Contamination
Int. J. Environ. Res. Public Health 2006, 3(2), 202-208; doi:10.3390/ijerph2006030024
Received: 6 February 2006 / Accepted: 2 June 2006 / Published: 30 June 2006
Cited by 3 | PDF Full-text (506 KB) | HTML Full-text | XML Full-text
Abstract
Recent advances in the use of polymeric materials for the remediation of phosphate from aqueous systems, including biological environments, have prompted the use of computational techniques to determine which methods are feasible to model such complex systems and to model the mechanism of
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Recent advances in the use of polymeric materials for the remediation of phosphate from aqueous systems, including biological environments, have prompted the use of computational techniques to determine which methods are feasible to model such complex systems and to model the mechanism of binding action. In particular, Sevelamer Hydrochloride (Renagel®) is used as our model polymer. A relatively simple system is constructed with a dimer of Sevelamer Hydrochloride and four phosphate ions used for capture. This work reports on molecular dynamics and Monte Carlo simulations used to determine average structure, and points of intermolecular interaction, and calculate changes in volume after the successful capture of phosphate in our model. Our resulting volume changes are of the order of 20-25%, in comparison to experimental swelling measurements on similar systems, which have an average swelling of 50-60% in aqueous media. Full article
Open AccessArticle Effect of Low Quality Effluent from Wastewater Stabilization Ponds to Receiving Bodies, Case of Kilombero Sugar Ponds and Ruaha River, Tanzania
Int. J. Environ. Res. Public Health 2006, 3(2), 209-216; doi:10.3390/ijerph2006030025
Received: 21 December 2005 / Accepted: 31 May 2006 / Published: 30 June 2006
Cited by 3 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
A study was conducted in a sewage system at Kilombero Sugar Company to review its design, configuration, effectiveness and the quality of influent and effluent discharged into the Ruaha river (receiving body). The concern was that, the water in the river, after effluent
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A study was conducted in a sewage system at Kilombero Sugar Company to review its design, configuration, effectiveness and the quality of influent and effluent discharged into the Ruaha river (receiving body). The concern was that, the water in the river, after effluent has joined the river, is used as drinking water by villages located downstream of the river. Strategic sampling at the inlet of the oxidation pond, at the outlet and in the river before and after the effluent has joined the receiving body (river) was undertaken. Samples from each of these locations were taken three times, in the morning, noon and evening. The sample were then analysed in the laboratory using standard methods of water quality analysis. The results showed that the configuration and or the layout of the oxidation ponds (treatment plant) were not in accordance with the acceptable standards. Thus, the BOD5 of the effluent discharged into the receiving body (Ruaha River) was in the order of 41 mg/l and therefore not meeting several standards as set out both by Tanzanian and international water authorities. The Tanzanian water authorities, for example, requires that the BOD5 of the effluent discharged into receiving bodies be not more that 30 mg/l while the World Health Organization (WHO) requires that the effluent quality ranges between 10 – 30 mg/l. The paper concludes that proper design of treatment plants (oxidation ponds) is of outmost importance especially for factories, industries, camps etc located in rural developing countries where drinking water from receiving bodies like rivers and lakes is consumed without thorough treatment. The paper further pinpoint that both owners of treatment plants and water authorities should establish monitoring/management plan such that treatment plants (oxidation ponds) could be reviewed regarding the change on quantity of influent caused by population increase. Full article

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