Ochratoxins—Food Contaminants: Impact on Human Health

Ochratoxins are secondary metabolites of Aspergillus and Penicillium, that are hazardous to health through contamination of dietary foods. Ochratoxin A (OTA) remains the single most potent member of this group of mycotoxins. OTA has a long half-life in humans and is thus easily detected in serum. Dietary intake studies have confirmed link between endemic nephrotoxicity in humans to their daily household intake of OTA. OTA has been reported to contribute to endemic nephrotoxicity and carcinogenicity in humans and animals. OTA produces renal tumours, DNA adducts and chromosomal aberrations in kidneys. OTA may be embryotoxic, teratogenic, and immunotoxic only at doses higher than those causing nephrotoxicity. The incidence of endemic nephrotoxicity has been mostly reported in northeast Europe since the early fifties. Recent studies however have warned that OTA and other toxins, such as aristolochic acid, show very similar renal pathology. There is thus the need for thorough co-occurrence studies on toxin incidence

Implication du polymorphisme d’enzymes de métabolisation et/ou de réparation dans le suivi de travailleurs exposés au styrène, à des solvants, des pesticides ou à l’arsenic

Les cancérogènes environnementaux sont convertis, par des enzymes de métabolisation dits de phase I ou de fonctionnalisation) et des enzymes de phase II ou de conjugaison), en métabolites réactifs pouvant se fixer à l’ADN. La plupart de ces enzymes sont polymorphes : le polymorphisme1 génétique est la base de la susceptibilité individuelle. Il est défini comme une différence par rapport au gène de référence, observée chez au moins 1 % des individus. Pour des expositions équivalentes, deux individus de même poids, même âge, même sexe peuvent avoir des taux plasmatiques2 de toxiques ou de métabolites variant de 1 à 1000 s’expliquant par des capacités d’absorption, de métabolisation et d’élimination différentes régulées génétiquement. La réponse toxique d’un individu vis-à-vis d’un contaminant va dépendre de ses capacités à transporter la substance, à la métaboliser et à réparer les lésions initiales sur l’ADN. Les enzymes de réparation sont aussi polymorphes. L’identification de certains variants alléliques3 de gène comme marqueurs de susceptibilité4 peut constituer un outil précoce de diagnostic et de pronostic

Exposition à des moisissures dans le milieu hospitalier et dans des usines de production de biogaz-Intérêt des protections individuelles et collectives

Les champignons filamenteux se développent de manière ubiquitaire sur de nombreux substrats organiques. Les spores se retrouvent dans les poussières et sont souvent inhalables. De plus en plus de données scientifiques pointent l’inhalation de moisissures comme cause d’allergie respiratoire ou cutanée aussi bien dans l’environnement (maisons insalubres) que dans le milieu du travail, notamment dans les industries de compostage de matière organique ou de fabrication de bioéthanol. La contamination peut aussi avoir lieu via les systèmes d’air conditionné. Les spores par elles-mêmes engendrent des effets toxiques à l’origine d’allergie. De plus, elles produisent des toxines. Les risques de développement de moisissures dans l’air inspiré sont bien connus en milieu hospitalier et plus particulièrement chez les personnes immunodépressives. Néanmoins, la présence des ces éléments fongiques en milieu de travail est responsable de rhinites, toux et problèmes dermatologiques, chez les travailleurs non immunodéprimés. Notre note portera sur la contamination de l’air en milieu hospitalier et dans un laboratoire de mycologie ainsi que sur les risques liés à l’air conditionné. Le dernier article relatera les effets subis par les travailleurs lors du compostage et de la fabrication de bioéthanol

Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Chicks

Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver

Response to Comments of Peter G. Mantle

The apparently high yield of testis tumors (25%) in rats exposed long-term to Ochratoxin A (OTA) is uninterpretable without data on tumor yield in unexposed rats. Conversely, our demonstration that prenatal exposure to OTA induces DNA adducts in the testes of newborn mice and the absence of these adducts in the testes of mice not exposed prenatally to OTA, is evidence for the presumptive carcinogenicity of OTA in the testis. Together with recent data showing that prenatal exposure to OTA depresses expression of DMRT1, a tumor suppressor gene in the testis, our findings suggest that OTA may be a cause of testicular cancer

Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the SupF Gene of the Mutation Reporter Plasmid Ps189

Ochratoxin A (OTA) is a mycotoxin that enhances renal tumor formation in the outer medulla of male rat kidney. Direct DNA damage and subsequent mutagenicity may contribute to these processes. In this study we have determined whether OTA in the absence or presence of activated rat liver microsomes (RLM) or redox-active transition metals (Fe(III) or Cu(II)) causes promutagenic DNA damage in the supF gene of the mutation reporter plasmid pS189 replicating in human Ad293 cells. In addition, we have assessed the mutagenicity of the hydroquinone metabolite (OTHQ) of OTA in the absence or presence of cysteine without added cofactors. Our results show that oxidation of OTA, either by RLM or by transition metal ions, activates OTA to a directly genotoxic mutagen(s). The Fe(III)/OTA system was the most potent mutagen in our experimental system, causing a 32-fold increase in mutant fraction (MF) above the spontaneous control MF. The Cu(II)/OTA system caused a 9-fold increase in MF, while a 6–10-fold increase in MF was observed for OTA in the presence of RLM. The OTHQ metabolite is also mutagenic, especially in the presence of cysteine, in which a 6-fold increase in MF was observed. Our data provide further insight into OTA bioactivation that may account for its in vivo mutagenicity in male rat kidney

Effect of cytostatic drugs on the sludge and on the mixed liquor characteristics of a cross-flow membrane bioreactor: Consequence on the process

The influence of cyclophosphamide and its principal metabolites (CPs) on the physicochemical properties of the mixed liquor of a cross-flow membrane bioreactor and the consequences for membrane fouling were investigated. The influence of CPs was determined by comparing the performance of two bioreactors running in parallel, MBR-CPs (with CPs) and MBR-control (without CPs). The physicochemical properties of the mixed liquor were characterized by soluble extracellular polymeric substances (soluble EPS content), particle size distribution and specific cake resistance. Results suggested that the CP toxicity altered the characteristics of the biological matrix of the activated sludge. Micro-organisms exposed to CPs showed higher endogenous respiration rates than MBR-control micro-organisms. The accumulation of soluble EPS and the formation of small particles (in MBR-CPs after cross-flow velocity was raised) increased the resistance to filtration. The fouling potential of the supernatant seemed to be linked more closely to the concentration of polysaccharides than of proteins and humic substances. Modifications of the membrane performance were observed. Under operating conditions, membrane fouling was faster in MBR-CPs than MBR-control. Moreover, the membrane played an important role in the permeate quality and the overall performance of the process, making possible the biological treatment of such an effluen

Cytoxicity and cytostatic drug removal in a membrane bioreactor from wastewater

The growing use of antineoplastic drugs in cancer therapy is an emerging issue in environmental research. The presence of the anticancer drug cyclophosphamide (CP) in municipal wastewater raises several environmental problems. Besides its cytotoxic effects, CP possesses teratogenic and mutagenic properties and is a known human carcinogen. The application of membrane bioreactor (MBR) technology was investigated with the aim of evaluating its potential for cytostatic drug bioremoval. The toxicity removal was assessed from biomarkers tests and related to the choice of the reactor operating conditions. The influence of sludge retention times (SRT) on CP removal was suited but not significant effects were found for variation of SRT from 50 days to 70 days. CP removal up to 80% was achieved under studied operating conditions. In front of such pollution, evidence has been made about the use of MBR. Our study proofed that advances wastewater treatment using a MBR provides a suitable process for lowering CP concentrations before discharge into the aqueous environment. However, a tertiary treatment is necessary for the complete elimination of toxicity

Cyclophosphamide removal from water by nanofiltration and reverse osmosis membrane

The rejection of cyclophosphamide (CP) by nanofiltration (NF) and reverse osmosis (RO) membranes from ultrapure (Milli-Q) water and membrane bioreactor (MBR) effluent was investigated. Lyophilization–extraction and detection methods were first developed for CP analysis in different water matrices. Experimental results showed that the RO membrane provided excellent rejection (>90%) under all operating conditions. Conversely, efficiency of CP rejection by NF membrane was poor: in the range of 20–40% from Milli-Q water and around 60% from MBR effluent. Trans-membrane pressure, initial CP concentration and ionic strength of the feed solution had almost no effect on CP retention by NF. On the other hand, the water matrix proved to have a great influence: CP rejection rate by NF was clearly enhanced when MBR effluent was used as the background solution. Membrane fouling and interactions between the CP and water matrix appeared to contribute to the higher rejection of CP

Cyclophosphamide removal by nanofiltration and reverse osmosis membranes - effect of water matrix properties

The rejection of cyclophosphamide (CP) by nanofiltration (NF) and reverse osmosis (RO) membranes from ultrapure (Milli-Q) water and membrane bioreactor (MBR) effluent was investigated. Experimental results showed that the RO membrane provided excellent rejection (>90%) under all operating conditions. Conversely, efficiency of CP rejection by NF membrane was poor: in the range of 20-40% from Milli-Q water and around 60% from MBR effluent. Trans-membrane pressure, initial CP concentration and ionic strength of the feed solution had almost no effect on CP retention by NF. On the other hand, the water matrix proved to have a great influence: CP rejection rate by NF was clearly enhanced when MBR effluent was used as the background solution. Membrane fouling and interactions between the CP molecule and water matrix appeared to contribute to the higher rejection of CP