In vitro biochemical assessment of mixture effects of two endocrine disruptors on INS-1 cells.

4-tert-Octylphenol (4-tOP) is a component of non-ionic surfactants alkylphenol polyethoxylates while triclosan (TCS) is an antibacterial present in personal care products. Both compounds can co-exist in environmental matrices such as soil and water. The mixture effects of these micropollutants in vitro remains unknown. INS-1 cells were exposed to 20 µM or 30 µM 4-tOP and 8 µM or 12.5 µM TCS as well as equimolar mixture of the chemicals (Mix) in total concentration of 12.5 µM or 25 µM for 48 h. Mitochondrial related parameters were investigated using high content analytical techniques. The cytotoxicity of the chemicals (IC50) varied according to TCS > Mix > 4-tOP. Increased glucose uptake and loss of mitochondrial membrane potential were recorded in TCS and Mix treated cells. Fold values of glucose-galactose assay varied according to dinitrophenol > TCS > 4-tOP > Mix in decreasing order of mitochondrial toxicity. The loss of the intracellular Ca2+ influx by all the test substances and Mix was not substantial whereas glibenclamide and diazoxide increased the intracellular Ca2+ influx when compared with the Blank. The recorded increase in Ca2+ influx by diazoxide which contrasted with its primary role of inhibiting insulin secretion need be re-investigated. It is concluded that the toxic effects of TCS and Mix but not 4-tOP on INS-1 cells was mitochondria-mediated.

Determination and ecological risk assessment of two endocrine disruptors from River Buffalo, South Africa.

4-tert-Octylphenol (4-tOP) and triclosan (TCS) are endocrine disruptors which have been detected in environmental matrices such as air, soil and water at ultra-low levels. Exposure to endocrine disruptors may account at least in part, for the global increase in the incidence of non-communicable diseases like cancers and diabetes and may also lead to an imbalance in the aquatic ecosystem. River Buffalo is an important natural resource in the Eastern Cape of South Africa serving more than half a million people. The presence of the two compounds in the river water hitherto unknown was investigated during winter seasons using solid-phase extraction and gas chromatography-mass spectrometric techniques. The sampling points differed by some physicochemical parameters. The concentration of 4-tOP ranged 0-755 ng/L, median value 88.1 ng/L while that of TCS ranged 0-1264.2 ng/L and the median value was 82.1 ng/L. Hazard quotient as an index of exposure risk varied according to daphnids Ëƒ fish Ëƒ algae for 4-tOP exposure while HQ for TCS exposure was algae > daphnids = fish showing that both compounds were capable of causing imbalance in the aquatic ecosystem. Graphical abstract.

Application of chromatographic techniques in the analysis of total nitrosamines in water.

The use of ozone, chloramine and chlorine dioxide for water treatment results in the formation N-nitrosamines in the treated water. These groups of chemicals and other nitrogen-containing compounds have been described as disinfection by-products (DBPs) which are known for their toxicity. Nitrosamines are a potential source of nitric oxide (NO) which can bind with metals present in the sample matrix leading to formation of metal - nitrosyl complexes and dissolved metals have the potential to increase the total nitrosamines in water. This phenomenon has not received the desired attention and determination of metal-nitrosyl complexes lack standard analytical technique. Chromatography linked to various detectors is the commonest of the techniques for nitrosamine analysis but it is beset with reduced sensitivity as a result of inappropriate choice of the column. Incidentally, chromatographic techniques have not been really adapted for the analysis of metal-nitrosyl complexes. Therefore, there is need for the survey of existing techniques vis-à-vis metal-nitrosamine analysis and to suggest possible areas for method optimization.

Environmental Water Pollution, Endocrine Interference and Ecotoxicity of 4-tert-Octylphenol: A Review.

4-tert-Octylphenol is a degradation product of non-ionic surfactants alkylphenol polyethoxylates as well as raw material for a number of industrial applications. It is a multimedia compound having been detected in all environmental compartments such as indoor air and surface waters. The pollutant is biodegradable, but certain degradation products are more toxic than the parent compound. Newer removal techniques from environmental waters have been presented, but they still require development for large-scale applications. Wastewater treatment by plant enzymes such as peroxidases offers promise in total removal of 4-tert-octylphenol leaving less toxic degradation products. The pollutant's endocrine interference has been well reported but more in oestrogens than in any other signalling pathways through which it is believed to exert toxicity on human and wildlife. In this paper we carried out a review of the activities of this pollutant in environmental waters, endocrine interference and relevance to its toxicities and concluded that inadequate knowledge of its endocrine activities impedes understanding of its toxicity which may frustrate current efforts at ridding the compound from the environment.

Lamivudine-Induced Liver Injury.

BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention. AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine. MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10-day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ-glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S-transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05. RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100 mg/kg. CONCLUSION: Lamivudine toxicity in rat liver appeared to be mediated by oxidative stress.