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Zwitterionic, cationic, and anionic per- and polyfluoroalkyl substances (PFAS) are increasingly reported in terrestrial and aquatic environments, but their inputs to agricultural lands are not fully understood. Here, we characterized PFAS in 47 organic waste products (OWP) applied in agricultural fields of France, including historical and recent materials. Overall, 160 PFAS from 42 classes were detected from target screening and homologue-based nontarget screening. Target PFAS were low in agriculture-derived wastes such as pig slurry, poultry manure, or dairy cattle manure (median ∑46PFAS: 0.66 μg/kg dry matter). Higher PFAS levels were reported in urban and industrial wastes, paper mill sludge, sewage sludge, or residual household waste composts (median ∑46PFAS: 220 μg/kg). Historical municipal biosolids and composts (1976–1998) were dominated by perfluorooctanesulfonate (PFOS), N-ethyl perfluorooctanesulfonamido acetic acid (EtFOSAA), and cationic and zwitterionic electrochemical fluorination precursors to PFOS. Contemporaneous urban OWP (2009–2017) were rather dominated by zwitterionic fluorotelomers, which represented on average 55% of ∑160PFAS (max: 97%). The fluorotelomer sulfonamidopropyl betaines (X:2 FTSA-PrB, median: 110 μg/kg, max: 1300 μg/kg) were the emerging class with the highest occurrence and prevalence in contemporary urban OWP. They were also detected as early as 1985. The study informs for the first time that urban sludges and composts can be a significant repository of zwitterionic and cationic PFAS.

Introduction:au Mali, il n'existe pas de données sur la prévalence des troubles mentaux. L´objectif de ce travail était de décrire les aspects cliniques et épidémiologiques des personnes hospitalisées en psychiatrie. Méthodes:notre étude était de type transversal conduite dans le service de psychiatrie du Centre Hospitalier Universitaire Point G sur 1105 dossiers de personnes hospitalisées pour trouble psychiatrique entre janvier 2014 et décembre 2018. Résultats:l'âge moyen était de 32,6± 11,1 ans avec des extrêmes de 13 et 82 ans. Le sexe masculin a représenté 83,8% (926/1105), 53,2% (588/1105) étaient célibataires, 18,8% (208/1105) n´avaient pas d´emploi et 28,2% (310/1105) avaient un niveau d'éducation primaire. Des antécédents de troubles psychiatriques étaient présents chez 74,0% (818/1105), la notion de consanguinité entre les parents était présente chez 22,7% (251/1105). L´utilisation de drogues était présente dans 42,9% (474/1105) dont le tabac avec 32,6% (361/1105), le cannabis avec 26,0% (287/1105) et/ou l'alcool avec 15,6% (172/1105). La demande de soins provenait des familles chez 87,5% (967/1105). L'agressivité était le motif de consultation le plus fréquent avec 44,5% (492/1105). Dans 67,8% (749/1105) des cas, le diagnostic était la schizophrénie, des troubles schizotypiques ou des troubles délirants. Les premiers recours aux soins étaient traditionnels avec 58,7% (649/1105). Conclusion:les personnes hospitalisées pour trouble psychiatrique de 2014 à 2018 étaient majoritairement jeunes et de sexe masculin avec un antécédent psychiatrique. Elles souffraient principalement de schizophrénie, de troubles schizotypiques et de troubles délirants.

International audience

International audience; BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies, the analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases. From this extensive database, it was considered important to engage in a detailed analysis so as to provide specific and strong evidences of ED while reflecting accurately the complexity of the response as well the multiplicity of adverse effects. An appropriate delineation of the scope of the analysis was therefore critical. Four effects namely, alterations of estrous cyclicity, mammary gland development, brain development and memory function, and metabolism, were considered to provide solid evidence of ED-mediated effects of BPA.

International audience

International audience; Modern agriculture often involves the use of pesticides to protect crops. These substances are harmful to target organisms (pests and pathogens). Nevertheless, they can also damage non-target animals, such as pollinators and entomophagous arthropods. It is obvious that the undesirable side effects of pesticides on the environment should be reduced to a minimum. Western honey bees (Apis mellifera) are very important organisms from an agricultural perspective and are vulnerable to pesticide-induced impacts. They contribute actively to the pollination of cultivated crops and wild vegetation, making food production possible. Of course, since Apis mellifera occupies the same ecological niche as many other species of pollinators, the loss of honey bees caused by environmental pollutants suggests that other insects may experience a similar outcome. Because pesticides can harm honey bees and other pollinators, it is important to register pesticides that are as selective as possible. In this manuscript, we describe a selection of methods used for studying pesticide toxicity/selectiveness towards Apis mellifera. These methods may be used in risk assessment schemes and in scientific research aimed to explain acute and chronic effects of any target compound on Apis mellifera.

International audience; Citrus plants are able to produce defense compounds such as coumarins and furanocoumarins to cope with herbivorous insects and pathogens. In humans, these chemical compounds are strong photosensitizers and can interact with medications, leading to the ``grapefruit juice effect''. Removing coumarins and furanocoumarins from food and cosmetics imply additional costs and might alter product quality. Thus, the selection of Citrus cultivars displaying low coumarin and furanocoumarin contents constitutes a valuable alternative. In this study, we performed ultra-performance liquid chromatography coupled with mass spectrometry analyses to determine the contents of these compounds within the peel and the pulp of 61 Citrus species representative of the genetic diversity all Citrus. Generally, Citrus peel contains larger diversity and higher concentrations of coumarin/furanocoumarin than the pulp of the same fruits. According to the chemotypes found in the peel, Citrus species can be separated into 4 groups that correspond to the 4 ancestral taxa (pummelos, mandarins, citrons and papedas) and extended with their respective secondary species descendants. Three of the 4 ancestral taxa (pummelos, citrons and papedas) synthesize high amounts of these compounds, whereas mandarins appear practically devoid of them. Additionally, all ancestral taxa and their hybrids are logically organized according to the coumarin and furanocoumarin pathways described in the literature. This organization allows hypotheses to be drawn regarding the biosynthetic origin of compounds for which the biogenesis remains unresolved. Determining coumarin and furanocoumarin contents is also helpful for hypothesizing the origin of Citrus species for which the phylogeny is presently not firmly established. Finally, this work also notes favorable hybridization schemes that will lead to low coumarin and furanocoumarin contents, and we propose to select mandarins and Ichang papeda as Citrus varieties for use in creating species devoid of these toxic compounds in future breeding programs.

Session 9 : Processing and Meat Chemical Safety; Nowadays, the control of the contamination of the food chain by toxic xenobiotics became a major safety issue given the strong relationships pointed out between chronic exposure to contaminants and pathologies such as cancers. This issue is particularly critical for animal-derived food products. The current methods operated to ensure this control are expensive, difficult to set up and unsuitable with frequent, regular and large-scale controls required to guarantee effectively the chemical safety of food. A new approach to trace-back these toxic xenobiotics along the food chain may consist in measuring markers of animal exposure to contaminants through omics approach. Among the various classes of metabolism end-products, we focused on volatile compounds which were identified as promising biomarkers to detect pathologies [11] or exposure to contaminants [10]. The present study aims to set up a SPME-MS fingerprinting method to point out the relevance of volatile metabolites in hepatic tissues as markers of chicken exposure to three types of xenobiotics: (i) an organochlorinated insecticide _lindane (γ-HCH), (ii) an environmental micropollutants_a mix of polychlorobiphenyls (PCBs), and (iii) an antibiotic _ ampicillin (Ampisol).

2193-1801 Severe, Sabine Marchand, Philippe Guiffard, Ingrid Morio, Floriane Venisseau, Anais Veyrand, Bruno Le Bizec, Bruno Antignac, Jean-Philippe Abadie, Jerome Journal Article Switzerland Springerplus. 2015 Jan 22;4:27. doi: 10.1186/s40064-015-0790-4. eCollection 2015.; International audience; PURPOSE: Invasive breast carcinoma is the most common cancer in women as in non-ovariectomised pet dogs, which are already identified as a valuable spontaneous preclinical model for that disease. Geographical and time trends suggest that environmental factors may play an important role in the etiology and pathogenesis of breast cancer. Persistent organic pollutants (POPs) fit perfectly with these trends and are known to interact with hormonal receptors implicated in breast cancer subtyping. The aim of this innovating study was to evaluate the interest of the companion dog model in assessing chemical exposure and breast cancer associations, in order to identify common etiological features with the human disease in a context of comparative oncology. METHODS: We monitored a hundred of molecules belonging to a large panel of POPs (dioxins, dioxin-like and non dioxin-like polychlorobisphenyls, organochlorine pesticides, brominated flame retardants, perfluorinated alkylated substances) in companion dogs diagnosed for mammary adenocarcinoma (n = 54) and non cancer controls (n = 47). RESULTS: All targeted chemical families were able to be detected in canine samples. We identified pollutants associated with mammary cancer belonging to the dioxin like-PCB family (notably PCB-118, -156, -105, -114) that were already pointed out in human epidemiological studies on breast cancer, and that fit with the fundamental role of the Aryl Hydrocarbon Receptor in the promotion of breast cancer. CONCLUSIONS: Similarities observed in the spontaneous dog model are very helpful to progress in interpretation of human breast cancer-environment relationships. This study provides a new insight focusing on this discrete but recurrent signature.

Toxicology of Reproductive and Endocrine System; This introductory chapter offers a basic overview of male reproduction, specifically the anatomy and physiology of the male reproductive system. Comprehension of normal anatomy and physiology is necessary to (1) fully understand the severity of toxicant-induced damage to structures and/or functions of the male reproductive system, (2) design more powerful experiments that analyze potential male reproductive toxicants, and (3) identify numerous potential targets of toxicants in the male reproductive system. This chapter begins with an overview of the hypothalamic-pituitary-testicular axis and its interaction with additional components of the male reproductive system. This is then followed by detailed presentation of the composition of the testis and the interrelationships of the testicular cells, spermatogenesis, the excurrent ducts that carry spermatozoa out of the testis, the accessory sex glands that supply the seminal plasma of semen, the cellular communication within the testis, the reproductive tract's development, and normal male sexual behavior. The chapter's conclusion emphasizes the foundational importance of the male reproductive system to desgining, conducting, and interpreting reproductive toxicology research.

International audience; Coumarins and furanocoumarins are secondary metabolites commonly found in citrus plants. These molecules are allelochemical compounds in plants that have controversial effects on humans, such as phototoxicity and the commonly described interactions with drugs, referred to as the ``grapefruit juice effect''. Thus, it is important to develop a reliable method to identify and quantitate the coumarins and furanocoumarins in citrus extracts. For this purpose, we herein describe an ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS)-based method. We first developed a rapid UPLC method (20 min) to separate the isomers of each furanocoumarin. A subsequent single ion monitoring MS detection method was performed to distinguish between the molecules, which were possibly coeluting but had different molecular weights. The method was successfully used to separate and quantitate 6 coumarins and 21 furanocoumarins in variable amounts within peel extracts (flayed and albedo) of 6 varieties of Citrus (sweet orange, lemon, grapefruit, bergamot, pummelo, and clementine). This method combines high selectivity and sensitivity in a rapid analysis and is useful for fingerprinting Citrus species via their coumarin and furanocoumarin contents.

Two cultivars of corn (Zea mays L., ‘HS7777’ Al‐sensitive and ‘C525‐M’ Al‐tolerant) were grown in nutrient solution at low aluminum (Al) activity to investigate the Al toxicity effects on their growth and mineral nutrition. With increasing levels of Al in the nutrient solution, root growth and root dry weights decreased for both cultivars, while higher reductions were found for ‘HS7777’. The concentrations of nitrogen (N), calcium (Ca), magnesium (Mg), potassium (K), and manganese (Mn) in the shoot and roots and iron (Fe) and zinc (Zn) in the shoot only decreased with the increase of Al levels in solution for both cultivars. This increase of Al toxicity increased the concentrations of carbon (C), copper (Cu), and boron (B) in the shoot and C, P, Fe, and Cu in the roots for both cultivars. High average concentrations of Ca, Mg, Mn, and Cu were found in the shoot of ‘HS7777’. No differences in the concentrations of Al, Ca, Mg, P, and Mn were observed in the roots of the two cultivars. Aluminum conc...

International audience; Chemoreception in insects is capable to detect highly diverse families of molecules like sugars, various bitter molecules, toxins, water, carbon dioxide and also a large panel of “xenobiotics”, which guide exploration for ecological niches.The taste neuronal elements are amazingly present in insect wings and this feature appears highly conserved in all the winged species of insect taxa.The functionality ofthe taste organs in wings is presently unknown andthis topology suggests an intriguing role that is not documented up to date. In this report we describe that the wing anterior margin neuronal nerve responds to sugars and bitter molecules through an increase of the cytosolic Ca2+ concentration that occurs in both pathways. As expected, the effects on AMPc levels are divergent for sugar and bitter signal transduction. This sensory modality strongly suggests that the pollinator insects “taste” molecules nebulized in theair vortex created by the wing beat during flight in close vicinity to flowers. This evolutionary conserved sensory organdissociates advantageously taste from ingestion avoiding toxicity by noxious substances.

Background Computer simulations provide a useful tool for bringing together diverse sources of information in order to increase understanding of the complex aetiology of drug use and related harm, and to inform the development of effective policies. In this paper, we describe SimAmph, an agent-based simulation model for exploring how individual perceptions, peer influences and subcultural settings shape the use of psychostimulants and related harm amongst young Australians. Methods We present the conceptual architecture underpinning SimAmph, the assumptions we made in building it, the outcomes of sensitivity analysis of key model parameters and the results obtained when we modelled a baseline scenario. Results SimAmph's core behavioural algorithm is able to produce social patterns of partying and recreational drug use that approximate those found in an Australian national population survey. We also discuss the limitations involved in running closed-system simulations and how the model could be refined to include the social, as well as health, consequences of drug use. Conclusion SimAmph provides a useful tool for integrating diverse data and exploring drug policy scenarios. Its integrated approach goes some way towards overcoming the compartmentalisation that characterises existing data, and its structure, parameters and values can be modified as new data and understandings emerge. In a companion paper (Dray et al., 2011), we use the model outlined here to explore the possible consequences of two policy scenarios.

Aims To show how the inclusion of agent-based modelling improved the integration of ethno-epidemiological data in a study of psychostimulant use and related harms among young Australians. Methods Agent-based modelling, ethnographic fieldwork, in-depth interviews and epidemiological surveys. Setting Melbourne, Perth and Sydney, Australia. Participants Club drug users in Melbourne, recreational drug users in Perth and street-based injecting drug users in Sydney. Participants were aged 18–30 years and reported monthly or more frequent psychostimulant use. Findings Agent-based modelling provided a specific focus for structured discussion about integrating ethnographic and epidemiological methods and data. The modelling process was underpinned by collective and incremental design principles, and produced ‘SimAmph’, a data-driven model of social and environmental agents and the relationships between them. Using SimAmph, we were able to test the probable impact of ecstasy pill-testing on the prevalence of harms—a potentially important tool for policy development. The study also navigated a range of challenges, including the need to manage epistemological differences, changes in the collective design process and modelling focus, the differences between injecting and non-injecting samples and concerns over the dissemination of modelling outcomes. Conclusions Agent-based modelling was used to integrate ethno-epidemiological data on psychostimulant use, and to test the probable impact of a specific intervention on the prevalence of drug-related harms. It also established a framework for collaboration between research disciplines that emphasizes the synthesis of diverse data types in order to generate new knowledge relevant to the reduction of drug-related harms.

In this paper we apply Agent-Based Modelling (ABM) to capture the complexity of the diffusion process depicted in Medical Innovation, the classic study on diffusion of a new drug Tetracycline by (Coleman, Katz, & Menzel, 1966). Based on our previous model with homogenous social agents, Gammanym (Ratna, Dray, Perez, Grafton, Newth, & Kompas, 2007), in this paper we further our analysis with heterogenous social agents who vary in terms of their degree of predisposition to knowledge. We also explore the impact of stage-dependent degrees of external influence from the change agent, pharmaceutical company in this case. Cumulative diffusion curves suggest that the pharmaceutical company plays a much weaker role in accelerating the speed of diffusion when a diffusion dynamics is explored with complex agents, defined as heterogenous agents under stage-dependent degrees of external influence. Although our exploration with groups of doctors with different combination of social and professional integration signifies the importance of interpersonal ties, our analysis also reveals that degree of adoption threshold or individual predisposition to knowledge is crucial for adoption decisions. Overall, our approach brings in fresh insights to the burgeoning policy literature exploring complexity, by providing necessary framework for research translation to policy and practice.

This chapter describes an agent-based model called SimDrugPolicing that explores the relative impact of three law enforcement strategies-standard patrol, hotspot policing, and problem-oriented policing-on an archetypal street-based illicit drug market. Using data from Melbourne (Australia), we simulate the relative effectiveness of these different drug law enforcement approaches. We examine the complex interactions between users, dealers, wholesalers, outreach workers and police to examine the relative effectiveness of the three drug law enforcement strategies, analyzing several outcome indicators such as the number of committed crimes, dealers 'and users 'cash, overdoses and fatal overdoses. Our results show that problem-oriented policing is the most effective approach to disrupting street level drug markets in a simulated urban environment. (Resume d'auteur)

Our paper examines how street-level drug markets adapt to a macro-level disruption to the supply of heroin, under three experimental conditions of street-level drug law enforcement: random patrol, hot-spot policing and problem-orientated policing. We utilize an agent-based model to explore the relative impact of abstractions of these three law enforcement strategies after simulating an ‘external shock’ to the supply of heroin to the street-level drug market. We use 3 years of data, which include the period of the ‘heroin drought’ in Melbourne (Australia) that commenced in late 2000 and early 2001, to measure changes in a selected range of crime and harm indicators under the three policing conditions. Our results show that macro-level disruptions to drug supply have a limited impact on street-level market dynamics when there is a ready replacement drug. By contrast, street-level police interventions are shown to vary in their capacity to alter drug market dynamics. Importantly, our laboratory abstraction of problem-orientated policing is shown to be the optimal strategy to disrupt street-level injecting-drug markets, reduce crimes and minimize harm, regardless of the type of drug being supplied to the market.

Mangrove forests, though essentially common and wide-spread, are highly threatened. Local societies along with their knowledge about the mangrove also are endangered, while they are still underrepresented as scientific research topics. With the present study we document local utilization patterns, and perception of ecosystem change. We illustrate how information generated by ethnobiological research can be used to strengthen the management of the ecosystem. This study was conducted in the Godavari mangrove forest located in the East-Godavari District of the state Andhra Pradesh in India, where mangroves have been degrading due to over-exploitation, extensive development of aquaculture, and pollution from rural and urbanized areas (Kakinada).One hundred interviews were carried out among the fisherfolk population present in two mangrove zones in the study area, a wildlife sanctuary with strong conservation status and an adjacent zone. Results from the interviews indicated that Avicennia marina (Forsk.) Vierh., a dominant species in the Godavari mangroves, is used most frequently as firewood and for construction. Multiple products of the mangrove included the bark of Ceriops decandra (Griff.) Ding Hou to dye the fishing nets and improve their durability, the bark of Aegiceras corniculatum (L.) Blanco to poison and catch fish, and the leaves of Avicennia spp. and Excoecaria agallocha L. as fodder for cattle. No medicinal uses of true mangrove species were reported, but there were a few traditional uses for mangrove associates. Utilization patterns varied in the two zones that we investigated, most likely due to differences in their ecology and legal status. The findings are discussed in relation with the demographic and socio-economic traits of the fisherfolk communities of the Godavari mangroves and indicate a clear dependency of their livelihood on the mangrove forest.Reported changes in the Godavari mangrove cover also differed in the two zones, with significantly less perceptions of a decrease in the protected area, as compared to the adjacent non-protected area. A posteriori comparisons between sequential satellite imagery (retrospective till 1977) and respondents that were at least 15 years back then, revealed a mangrove decrease which was however perceived to different extents depending on the area with which the fishermen were familiar. While local needs had not been incorporated in the existing policy, we created a framework on how data on ethnobotanical traditions, fishery-related activities and local people's perceptions of change can be incorporated into management strategies.

The Drug Policy Modelling Project aims to develop new tools for policy makers to improve the ways in which evidence is used. A number of modelling approaches have been explored, and this monograph outlines the complex system scientists work. The first section outlines how drug use and drug markets are complex phenomena. Approaches from complexity - dynamical systems models; network theory; and multi-agent systems - are then outlined. The third section describes the development of a multi-agent system (the model called SimDrug) followed by a summary of the preliminary results arising from the model. The monograph concludes with considerations of future development of SimDrug.

Une série d'essais a été conduite dans l'optique de cultiver de la canne a sucre sur une solution nutritive. Il s'agit de la seule méthode simple envisageable pour étudier l'effet de l'aluminium libre sur le développement racinaire. Une première partie a porté sur la production de 'plantules' de canne à sucre disposant de très peu de réserves trophiques et d'un système racinaire en tout début de développement. Nous avons recherché en second lieu à mettre au point une solution nutritive adaptée à la canne à sucre ainsi qu'à définir les modalités permettant de maîtriser à tout moment le niveau d'aluminium libre en solution. Cette étude débouche sur un protocole expérimental d'étude de l'influence de l'aluminium sur le développement racinaire, de la canne a sucre.

Au Sénégal, la contamination par l'aflatoxine des arachides en pré-récolte est dominante sur la contamination en post-résolte. La contamination en pré-récolte est largement due au déficit hydrique de fin de cycle rencontré dans les régions les plus sèches du Bassin arachidier. Dans le but de vérifier l'existence d'une réponse différentielle de génotypes plus ou moins résistants à la sécheresse, nous avons mesuré l'évolution et les relations existant entre certains indicateurs de résistance à l'aflatoxine dans différentes conditions environnementales et d'alimentation hydrique

Il existe quelques méthodes traditionnelles de lutte contre la contamination par l'aflatoxine, à savoir le "calage" du cycle végétatif en fonction de la saison des pluies (semis, récolte, précocité variétale), tri manuel, traitements contre les insectes du sol. L'efficacité de ces techniques (contraignantes) dépend des conditions climatiques de l'année de culture et des moyens du producteur. La meilleure stratégie consiste, pour l'auteur, à recourir à l'amélioration génétique de la résistance variétale au champignon Aspergillus flavus/parasiticus, à plusieurs niveaux : gousse, cuticule, graine. L'auteur analyse les mécanismes en cause et les divers types de résistance. Le dosage de la substance toxique a fait des progrès pour aider la sélection. Il faut trouver des génotypes capables de synthétiser des phytoalexines en conditions de sécheresse

Au nom du principe de precaution sanitaire, l'UE a edicte en 1998 une norme extremement restrictive en matiere de tolerance aflatoxine (2 µg d'aflatoxine B1 ou 4 µg pour la somme des 4 aflatoxines B1 + B2 + G1 + G2) dans les fruits secs destines a l'alimentation humaine. Mise en application depuis le 01/01/2001, sans progressivite, cette mesure met en peril les filieres d'exportation d'arachide de bouche, notamment celles des pays ACP, techniquement mal prepares pour reagir efficacement. Elle genere des surcouts importants de mise aux normes, de controle et de formation necessitant des moyens financiers consequents, ce qui implique une action conjointe des organisations internationales du commerce, de la sante et de l'education. Le Cirad cherche a tout mettre en oeuvre pour aider les pays producteurs les moins prepares a une reglementation aussi severe. (Resume d'auteur)

La sensibilité de deux ravageurs du cotonnier vis-à-vis de six matières actives a été mesurée en laboratoire et les droites de régression dose/mortalité ont été établies suivant la méthode Probit/Log de Finney. Les tests ont porté en outre sur l'association du fenvalérate avec chacun des organophosphorés à deux ratios différents : trois des associations ont montré des coefficients de toxicité intéressants

L'utilisation des herbicides en hévéaculture se répand. Leur emploi sans précaution provoque des dégâts en particulier la pulvérisation de MSMA sur le tronc entraîne des nécroses de l'écorce. Il faut absolument éviter de pulvériser du MSMA sur les troncs d'hévéa

Historique et situation actuelle de l'utilisation des produits phytosanitaires en régions chaudes

International audience; Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come. Genetic and environment factors deserve therefore more attention when dealing with regulatory limits, since among the general population, those who are at risk and will develop specific diseases are likely those bearing genetic predispositions. We have addressed these questions for the specific case of ochratoxin A in humans by investigating in Tunisia, county of Jelma, in four rural families forming a household of 21 persons all exposed to ochratoxin A in diet. Our results confirm that ochratoxin A induces chronic tubular nephropathy in humans and mainly point at those having the HLA haplotype A3, B27/35, DR7 to be more sensitive to the disease for quantitatively similar or lower exposure. Persons with such haplotype were found to bear chronic interstitial nephropathy with tubular karyomegalic cells while others were apparently healthy. Godin et al. (1996) in France have also found in sibling (a sister and her brother from urban area) that have similar HLA haplotype B35-patern, OTA-related renal tubulopathy with mild proteinuria including beta2-microglobulinuria. Several mechanisms are discussed that could be put ahead to explain how the HLA haplotype could lead to tubular cells lyses and renal failure. In the mean time it is urgent to search for mass screening biomarkers for mycotoxins in humans and related genetic factors to set-up more appropriate regulation.