Dietary exposure to aflatoxins, ochratoxin A and deoxynivalenol from a total diet study in an adult urban Lebanese population.

Exposure to mycotoxins may be associated with carcinogenic, immunosuppressant and estrogenic effects. In the Middle-East, studies investigating food contamination and dietary exposure to mycotoxins are particularly scarce. This study aims at evaluating the dietary exposure of an adult Lebanese urban population to four mycotoxins (AFB1, AFM1, OTA, DON) classified as priority food contaminants by the WHO. Dietary exposure assessment was performed by means of the total diet study approach. Average and excessive consumer exposure estimates (p95) were calculated and compared with appropriate toxicological reference values (TRVs). Average dietary exposure levels to OTA and DON represented 29.9% and 156.8% of the respective TRVs, with the p95 exposure estimates approaching or exceeding the TRVs for these mycotoxins (95.1% and 355.8%, respectively). Based on the mean dietary exposure level to AFB1, cancer risk was estimated at 0.0527-0.0545cases/100,000persons/year, while mean exposure to AFM1 was associated with a population risk of 0.0018-0.0027cases/100,000persons/year. The study's findings place Lebanon among countries that are highly exposed to mycotoxins through the diet and call for larger-scale studies aiming at providing a comprehensive assessment of the dietary exposure of the Lebanese population to mycotoxins as well as to other food contaminants.

Effects of beauvericin, enniatin b and moniliformin on human dendritic cells and macrophages: an in vitro study.

The aim of this study was to assess the in vitro effects of emerging mycotoxins beauvericin, enniatin B and moniliformin on human dendritic cells and macrophages. Beauvericin and enniatin B were cytotoxic on these cells. IC50 were equal to 1.0 µM, 2.9 µM and 2.5 µM beauvericin for immature dendritic cells, mature dendritic cells and macrophages, respectively. IC50 were equal to 1.6 µM, 2.6 µM and 2.5 µM for immature dendritic cells, mature dendritic cells and macrophages exposed to enniatin B, respectively. Effects on the differentiation process of monocytes into macrophages or into immature dendritic cells as well as effects on dendritic cells maturation have been studied. The differentiation process of monocytes into immature dendritic cells was not disturbed in the presence of beauvericin. Dendritic cells exposed to beauvericin during the maturation process presented a decrease of CCR7 expression and an increase of IL-10 secretion. Monocytes exposed to beauvericin during the differentiation process into macrophages presented a decrease of endocytosis ability. The differentiation process of monocytes into immature dendritic cells was not disturbed in the presence of enniatin B. Dendritic cells exposed to enniatin B during the maturation process presented a decrease of expression of the maturation makers CD80, CD86 and CCR7 and an increase of IL-10 secretion. Monocytes exposed to enniatin B during the differentiation process into macrophages presented a decrease of endocytosis ability and an increase of CD71. CD1a expression and endocytosis capacity were decreased on immature dendritic cells exposed to moniliformin. Monocytes-derived macrophages exposed to moniliformin during the differentiation process presented a decrease of endocytosis ability, and a decrease of CD71 and HLA-DR expression. According to these results, immunological disorders could be observed on human after ingestion of these alimentary toxins.

Co-exposure of Fusarium mycotoxins: in vitro myelotoxicity assessment on human hematopoietic progenitors.

Mycotoxins such as beauvericin (BEA), deoxynivalenol (DON), enniatin B (ENB), fumonisin B1 (FB1), T-2 toxin and zearalenone (ZEA) can co-occur in food commodities. This aim of this study was to assess the myelotoxicity of these mycotoxins in couple using in vitro human granulo-monocytic (Colony Forming Unit-Granulocyte and Macrophage, CFU-GM) hematopoietic progenitors. Clonogenic assays have been performed in the presence of the following couples of fusariotoxins: DON + BEA, DON + FB1, DON + T-2, DON + ZEA, T-2 + ZEA and BEA + ENB. Co-exposure of human CFU-GM to DON + BEA resulted in synergic myelotoxic effects. The combination of DON + T-2 presented additive or synergic myelotoxic effects. The couples DON + ZEA, T-2 + ZEA and BEA + ENB had additive myelotoxic effects, while the combination of DON + FB1 showed antagonist myelotoxic effects. These in vitro results suggested that the simultaneous presence of mycotoxins in food commodities and diet may be more myelotoxic than the presence of one mycotoxin alone. Diminution of hematopoietic progenitors could give rise to a decrease number of mature blood cells, inducing agranulocytosis and/or thrombocytopenia and in severe cases aplastic anemia.

Evaluation of shellfish consumption in Nha Trang City, Southern coastal Vietnam.

INTRODUCTION: Shellfish consumption may be a significant pathway to food contaminants such as heavy metals, pesticides and phycotoxins. Currently, little information exists about consumption of shellfish in Vietnam. Such data could be of interest in terms of nutritional value or risk assessment. METHODS: Consumption of shellfish was assessed using a food frequency questionnaire and validated by a 7-day recall method. Approximately 1% of the city population of Nha Trang was selected yielding a final sample of 440 participants. The participants were above 18 years of age, in apparently good health and were shellfish consumers. RESULTS: In South coastal Vietnam, the types of shellfish most consumed are green mussel, squid, crab and shrimp. The mean consumption rates of the bivalves, crustaceans, gastropods, cephalopods, echinoderms and all shellfish combined were 39.3, 20.9, 16.4, 11.2, 0.3 and 88.1 g/person/day, respectively. The consumption rate was slightly higher in the age group of 30-54 years, than in the younger (18-29 years) and older (55 years and above) age groups. Shellfish is essentially purchased in the markets and temporary markets, and mostly consumed during the dry season. CONCLUSION: Shellfish consumption in the Southern coastal region of Vietnam is high compared to consumption levels in other countries; it is also high compared to consumption levels of Vietnamese emigrants. Such data may be useful for further investigation on nutrition perspectives and in term of risk assessment of shellfish contaminants.

In vitro myelotoxicity assessment of the emerging mycotoxins Beauvericin, Enniatin b and Moniliformin on human hematopoietic progenitors.

The aim of this study was to screen potential myelotoxicity of the emerging mycotoxins Beauvericin, Enniatin b and Moniliformin using human hematopoietic progenitor clonogenic assays. Depending on mycotoxins, inhibitory effects on proliferation of white blood cells progenitors (CFU-GM), platelet progenitors (CFU-MK) and red blood cells progenitors (BFU-E) have been detected at various concentrations. Beauvericin was cytotoxic at 32µM, 3.2µM and 6.4µM, had no effect on proliferation in the presence of 0.032µM, 0.16µM and 0.064µM, and the IC(50) was equal to 3.4µM, 0.7µM and 3.7µM for CFU-GM, CFU-MK and BFU-E, respectively. Enniatin b was cytotoxic at 6µM, 1.8µM and 5µM, had no effect on proliferation in the presence of 1µM, 1.1µM and 1.2µM and the IC(50) was equal to 4.4µM, 1.3µM and 3.3µM for CFU-GM, CFU-MK and BFU-E, respectively. Moniliformin was not cytotoxic at tested concentrations for CFU-GM and CFU-MK and cytotoxic at 10µM for BFU-E, had no effect on proliferation in the presence of 5µM, 0.1µM and 0.1µM and the IC(50) was equal to 31µM, 39µM and 4.1µM for CFU-GM, CFU-MK and BFU-E, respectively. Inhibition of the BFU-E differentiation has been observed in the presence of Enniatin b or Moniliformin. For the three mycotoxins, variation of distribution of CFU-MK colonies according to their size has been observed. These in vitro effects may be responsible for in vivo hematological troubles in case of consumption of contaminated commodities. In vivo studies have to be performed to test this hypothesis.

Evaluation of Shellfish Consumption in Nha Trang City, Southern Coastal Vietnam

Introduction: Shellfish consumption may be a significant pathway to food contaminants such as heavy metals, pesticides and phycotoxins. Currently, little information exists about consumption of shellfish in Vietnam. Such data could be of interest in terms of nutritional value or risk assessment. Methods: Consumption of shellfish was assessed using a food frequency questionnaire and validated by a 7-day recall method. Approximately 1% of the city population of Nha Trang was selected yielding a final sample of 440 participants. The participants were above 18 years of age, in apparently good health and were shellfish consumers. Results: In South coastal Vietnam, the types of shellfish most consumed are green mussel, squid, crab and shrimp. The mean consumption rates of the bivalves, crustaceans, gastropods, cephalopods, echinoderms and all shellfish combined were 39.3, 20.9, 16.4, 11.2, 0.3 and 88.1 g/person/day, respectively. The consumption rate was slightly higher in the age group of 30-54 years, than in the younger (18-29 years) and older (55 years and above) age groups. Shellfish is essentially purchased in the markets and temporary markets, and mostly consumed during the dry season. Conclusion: Shellfish consumption in the Southern coastal region of Vietnam is high compared to consumption levels in other countries; it is also high compared to consumption levels of Vietnamese emigrants. Such data may be useful for further investigation on nutrition perspectives and in term of risk assessment of shellfish contaminants.

Dietary exposure to essential and toxic trace elements from a Total diet study in an adult Lebanese urban population.

This study assesses, by the Total diet study approach, the adequacy of micronutrient intake (Co, Cu, Fe, Mn, Ni, Zn) and the dietary exposure of a Lebanese adult urban population to two toxic elements (Cd, Pb). The foods that made up the average 'total diet' were derived from a previous individual consumption survey. A total of 1215 individual foods were collected, prepared and cooked prior to analysis. Analytical quantification was performed using inductively coupled plasma mass spectrometry. Average daily intakes of Co (11.4 microg/day), Cu (1104.19 microg/day), Fe (13.00 mg/day), Mn (2.04 mg/day), Ni (126.27 microg/day) and Zn (10.97 mg/day) were below toxicological reference values and were found to satisfy nutritional recommendations, except for manganese in men and iron in women. Average dietary exposure to Pb and Cd represented 3.2% and 21.7% of the respective provisional tolerable weekly intakes. Estimates of dietary intakes of iron appeared to be inadequate for 63% of adult women. These findings should constitute a current measure of assessing the adequacy and safety of foods consumed in Lebanon and may be a basis for future monitoring studies.

Stem cells in myelotoxicity.

Myelotoxicity describes bone marrow failure due to adverse effect of xenobiotic on hematopoiesis. Hematopoiesis is a complex system in which pluripotent hematopoietic stem cells (PHSCs) differentiate into many highly specialized circulating blood cells involving the interaction of many cell types as well as the interaction of local and systemic growth factors. With respect to blood cell formation, two functional systems must be considered: the hematopoietic stem cells (PHSCs) and the progenitor cells, on one hand, and the stromal cells, which constitute the hematopoietic environment niche, on the other hand. There are three types of assays for hematopoietic progenitor clonogenic assays useable in myelotoxicology: CFU-GM assay for Colony Forming Unit Granulocyte and Macrophage, BFU-E assay for Burst Forming Unit Erythroid, and CFU-MK assay for Colony Forming Unit Megakaryocyte from several species as well as from murine as from mammalian and human. Clonogenic assays have been used to detect myelotoxicity induced by chemicals, drug, food and environmental contaminants. Designs and applications are described in this review.

T-2 toxin inhibits the differentiation of human monocytes into dendritic cells and macrophages.

The aim of this work was to study the in vitro effect of T-2 toxin on human monocyte differentiation into macrophages and dendritic cells. Cytotoxicity of T-2 toxin on monocytes, on monocytes in differentiation process into macrophages or dendritic cells, and on immature dendritic cells and macrophages was evaluated to determine IC50. Monocytes are more sensitive to T-2 toxin than to differentiate cells. IC50 were equal to 0.11 nM for monocyte, to 45 and 30 nM for monocyte during differentiation process for 24 and 48 h of incubation, respectively, to 38 and 20 nM for immature dendritic cells after 24 and 48 h of incubation, and to 22 and 20 nM for macrophages after 24 and 48 h of incubation. T-2 toxin effects on monocyte differentiation process into macrophages have been explored: according to phenotypic expressions (CD71, CD14, CD11a, CD80, CD86, HLA-DR and CD64), endocytic capacity, phagocytosis, burst respiratory activity and TNF-alpha secretion. In the presence of 10 nM of T-2 toxin (no cytotoxic concentration), CD71 expression is downregulated compared to control. Endocytosis and phagocytosis capacities are less effective as burst respiratory activity and TNF-alpha secretion. Monocyte differentiation process into dendritic cells in the presence of 10 nM T-2 toxin is also markedly disturbed. Expression of CD1a (specific dendritic cells marker) is downregulated while that of CD14 (specific monocyte marker) is upregulated. CD11a, CD80, CD86, HLA-DR and CD64 expressions did not change. These results show that T-2 toxin disturbs human monocytes differentiation process into macrophages and dendritic cells. These results could significantly contribute to immunosuppressive properties of this alimentary toxin.

Application of human CFU-Mk assay to predict potential thrombocytotoxicity of drugs.

Megakaryocytopoiesis gives rise to platelets by proliferation and differentiation of lineage-specific progenitors, identified in vitro as Colony Forming Unit-Megakaryocytes (CFU-Mk). The aim of this study was to refine and optimize the in vitro Standard Operating Procedure (SOP) of the CFU-Mk assay for detecting drug-induced thrombocytopenia and to prevalidate a model for predicting the acute exposure levels that cause maximum tolerated decreases in the platelets count, based on the correlation with the maximal plasma concentrations (C max) in vivo. The assay was linear under the SOP conditions, and the in vitro endpoints (percentage of colonies growing) were reproducible within and across laboratories. The protocol performance phase was carried out testing 10 drugs (selected on the base of their recognised or potential in vivo haematotoxicity, according to the literature). Results showed that a relationship can be established between the maximal concentration in plasma (C max) and the in vitro concentrations that inhibited the 10-50-90 percent of colonies growth (ICs). When C max is lower than IC10, it is possible to predict that the chemicals have no direct toxicity effect on CFU-Mk and could not induce thrombocytopenia due to bone marrow damage. When the C max is higher than IC90 and/or IC50, thrombocytopenia can occur due to direct toxicity of chemicals on CFU-Mk progenitors.

Activity concentrations and mean annual effective dose from gamma-emitting radionuclides in the Lebanese diet.

Since the primary factor contributing to the internal effective dose in the human organism is contaminated food, the control of radionuclides in food represents the most important means of protection. This study was conducted to determine the levels of the dietary exposure of the Lebanese population to gamma-emitting radioisotopes. The activity concentrations of gamma-emitting radioisotopes have been measured in food samples that represent the market basket of an adult urban population in Lebanon. The artificial radionuclide (137)Cs was measured above detection limits in only fish, meat and milk-based deserts. The most abundant natural radionuclide was 40K (31-121 Bq kg(-1)), with the highest content in fish and meat samples. The annual mean effective dose contributed by 40K in the reference typical diet was estimated equal to 186 microSv y(-1), a value reasonably consistent with findings reported by several other countries.

Dietary exposure to lead, cadmium, mercury and radionuclides of an adult urban population in Lebanon: a total diet study approach.

Human exposure to toxic chemicals is suspected of being responsible for a wide range of human health disorders. This study is the first in Lebanon to evaluate the dietary exposure of an adult urban population to three heavy metals (lead, cadmium and mercury) and to radionuclides. Exposure assessment was performed by means of the total diet study approach as recommended by the Word Health Organization. Five 'total diets' were collected during 2003-04. Average and maximal consumer exposure estimates to heavy metals were calculated and compared with appropriate reference values and with intakes reported from other countries. The average dietary intakes of lead, cadmium and mercury represented 7, 17 and 5.6%, respectively, of the appropriate provisional tolerable weekly intakes (PTWI). The mean dietary intake of methylmercury represented 17.5% of the appropriate PTWI. Cs-134 and I-131 were not detected in any of the food samples. Traces of Cs-137 were only found in five food samples. The exposure assessment conducted places Lebanon among countries least exposed to heavy metals through the diet and it highlights the safety of the food supply from radioactive contamination.

Improvement of human dendritic cell culture for immunotoxicological investigations.

A toxic injury such as a decrease in the number of immature dendritic cells caused by a cytotoxic effect or a disturbance in their maturation process can be responsible for immunodepression. There is a need to improve in vitro assays on human dendritic cells used to detect and evaluate adverse effects of xenobiotics. Two aspects were explored in this work: cytotoxic effects of xenobiotics on immature dendritic cells, and the interference of xenobiotics with dendritic cell maturation. Dendritic cells of two different origins were tested. Dendritic cells obtained either from umbilical cord blood CD34(+) cells or, for the first time, from umbilical cord blood monocytes. The cytotoxicity assay on immature dendritic cells has been improved. For the study of the potential adverse effects of xenobiotics on the maturation process of dendritic cells, several parameters were selected such as expression of markers (CD86, CD83, HLA-DR), secretion of interleukins 10 and 12, and proliferation of autologous lymphocytes. The relevance and the efficiency of the protocol applied were tested using two mycotoxins, T-2 toxin and deoxynivalence, DON, which are known to be immunosuppressive, and one phycotoxin, domoic acid, which is known not to have any immunotoxic effect. Assays using umbilical cord monocyte dendritic cell cultures with the protocol defined in this work, which involves a cytotoxicity study followed by evaluation of several markers of adverse effects on the dendritic cell maturation process, revealed their usefulness for investigating xenobiotic immunotoxicity toward immune primary reactions.

In vitro effects of trichothecenes on human dendritic cells.

The aim of this work was to study the in vitro effects of trichothecenes on human dendritic cells. Trichothecenes are mycotoxins produced by fungi such as Fusarium, Myrothecium, and Stachybotrys. Two aspects have been explored in this work: the cytotoxicity of trichothecenes on immature dendritic cells to determine IC 50 (inhibition concentration), and the effects of trichothecenes on dendritic cell maturation process. Two mycotoxins (T-2 and DON) known to be immunotoxic have been tested on a model of monocyte-derived dendritic cells culture. Cytotoxic effects of T-2 toxin and DON on immature dendritic cells showed that DON is less potent than T-2 toxin. The exposure to trichothecenes during dendritic cell maturation upon addition of LPS or TNF-alpha markedly inhibited the up-regulation of maturation markers such as CD-86, HLA-DR and CCR7. Features of LPS or TNF-alpha -mediated maturation of dendritic cells, such as IL-10 and IL-12 secretions and endocytosis, were also impaired in response to trichothecenes treatment. These results suggest trichothecenes have adverse effects on dendritic cells and dendritic cell maturation process.

Safety of Oxygreen, an ozone treatment on wheat grains. Part 2. Is there a substantial equivalence between Oxygreen-treated wheat grains and untreated wheat grains?

The Oxygreen process is a new process based on wheat grain treatment by ozone (produced in situ), in a closed sequential batch reactor. The Oxygreen process offers a close, homogeneous, and controlled contact between the gas and the grain. It is proposed for use for wheat grain decontamination (insects, fungi, bacteria, mycotoxins, pesticides). It takes place in classical milling diagram, and occurs after grain cleaning and before milling. The aim of the study reported here was to determine if Oxygreen treatment could induce in the grain the formation of processing-related compounds, and if these compounds are specific or could be recognized as classical modifications already used in the cereal industry (milling, baking). Studies were performed in order to evaluate any effect of Oxygreen treatment on vitamins, ferulic acid, phytates, proteins, carbohydrates, and lipids. It was concluded that there was no detectable substantial difference between ozone-treated grains and the untreated ones, although some quantitative differences can occur. The more detectable differences concern concentration of free sugars, and inhibition of some oxidative enzymes. These quantitative differences are very slight compared to the modifications that occur in dough, after addition of oxidative products directly in flour, or during kneading and dough fermentation.

Safety of Oxygreen, an ozone treatment on wheat grains. Part 1. A four-week toxicity study in rats by dietary administration of treated wheat.

The Oxygreen process is a new treatment approved by The French Food Safety Authority (AFSSA) as a processing aid for flour quality improvement, based on treatment by ozone, in a closed sequential batch reactor. This treatment takes place in the classical milling sequence, after the grain-cleaning step and before milling. The Oxygreen process could also be used for its properties in wheat grain decontamination (insects, fungi, bacteria, mycotoxins, storage insecticides residues). The aim of this study was to determine if Oxygreen treatment could induce in the grain the formation of processing-related substances, able to provoke adverse effects, after ingestion of the wheat and/or derived products, and to establish the safety of the Oxygreen process for animals and consumers. A four-week toxicity study, according to OECD guideline No. 407, was performed on Dark agouti rats fed exclusively with wheat grains, treated or untreated with Oxygreen. Clinical, haematological, blood biochemical, urinary and histopathological parameters were investigated during the study. The few modifications observed in animals given treated wheat were an increase of rectal temperature in females, a slight decrease of calcium concentration in males and slight decrease of certain blood cell number without clinical significances. This work shows that wheat treated by Oxygreen does not induce adverse effects in Dark agouti rats after oral administration. Therefore wheat and derived products from wheat, after Oxygreen treatment on grain, could be considered as safe for the consumer.

Myelotoxicity of trichothecenes and apoptosis: an in vitro study on human cord blood CD34+ hematopoietic progenitor.

Previous studies have revealed that hematological disorders associated with trichothecenes intoxication in humans could result from hematopoiesis inhibition. The most frequent and potent trichothecene mycotoxins are T-2 toxin and deoxynivalenol (DON), respectively. Apoptosis induction by these two toxins was investigated in vitro on human hematopoietic progenitors (CD34+ cells). Hoechst coloration, DNA fragmentation and annexin-V/PI labeling in flow cytometry showed that T-2 toxin, in contrast to DON, induced apoptosis in CD34+ cells. T-2 toxin effect was dose- and time-dependent with a significant increase of apoptotic cells as early as 3h after incubation at 10(-7) M and a maximum reached at 12 h. This observation evidenced the high sensitivity of hematopoietic progenitors to T-2 toxin. The inhibition of T-2 toxin-induced apoptosis by a pan-caspase inhibitor (Z-VAD-fmk) suggested the involvement of caspases. The proportional increase of caspase-3 specific activity (DEVDase) with T-2 toxin concentration confirmed its role in the process. After incubation of CD34+ cells with T-2 toxin, in conditions that induced apoptosis, clonal expansion of granulo-monocytes, erythrocytes and megakaryocytes precursors was dose-dependently inhibited. The hematological effects observed in T-2 toxin mycotoxicosis could then be assigned to hematopoiesis inhibition by apoptosis. Different mechanisms that need to be further elucidated are involved in DON myelotoxicity.

Haematotoxicity of trichothecenes.

Human toxicosis induced by consumption of foodstuffs contaminated with trichothecenes presents one common major symptom: a haematological perturbation manifesting principally as thrombocytopenia and leukopenia. The patients have rapidly progressing coagulation problems, and compromised resistance to infections. Consequently, they are subject to septicaemia and massive haemorrhages. In horses, cattle, poultry, cats, mice and guinea pigs, subacute and subchronic ingestion of trichothecenes causes a decrease of circulating blood cells frequently associated with bone marrow failure. The origins of haematological effects observed in Fusarium toxin intoxications have been elucidated using in vitro tests. Haematopoietic progenitors are the main target of trichothecenes. Deoxynivalenol (DON) is the least myelotoxic and T-2 the most. As circulating blood cells present a less important sensitivity to these toxins, haematological troubles observed in toxicosis are due to myelotoxicity of these toxins.

Inhibition of CFU-E/BFU-E and CFU-GM colony growth by cyclophosphamide, 5-fluorouracil and taxol: development of a high-throughput in vitro method.

The major side effect of anticancer drugs is damage to the hematopoietic system. These compounds may interfere with cell proliferation and differentiation in different blood lineages causing many diseases such as neutropenia, aplastic anaemia or trombocytopenia. The clonogenic assays are useful in vitro tools for evaluating and predicting acute xenobiotics myelotoxicity. A miniaturisation of these assays, in order to reduce costs and increase the number of compounds that could be tested, is under investigation. The in vitro sensitivity of human burst-forming unit erythroid (BFU-E) and colony-forming unit granulocyte-macrophage (CFU-GM) to three anticancer drugs: cyclophosphamide (CTX), 5-fluorouracil (5-FU) and taxol (TAX) was evaluated both in 35 mm plate and 96-well plate systems and the dose-response curves, IC50 values and IC90 values were compared. The correlation between in vitro data and clinical plasma levels confirms that severe hematotoxicity is the primary adverse effect of these drugs with an evident selectivity on erythroid progenitors for cyclophosphamide. IC50 and IC90 values, calculated on the basis of results obtained with the traditional assay, correlate with those obtained in microplate, as well as the dose-response curves, indicating that the 96 well plate assay could be a useful and reliable tool for high-throughput screening in early stages of drug development.

Do trichothecenes reduce viability of circulating blood cells and modify haemostasis parameters?

This manuscript describes the results of experiments conducted using human blood cells to determine the ability of T-2 toxin and DON to cause changes in clotting time, platelet aggregation, red blood cell haemolysis, RBC glucose content, lactate release, glutathione depletion, as well as white blood cell viability. In vitro results showed that haemostasis parameters and erythrocytes were not affected at concentrations able to induce inhibition of haematopoietic progenitor proliferation. In the presence of 10(-8) M and 10(-6) M T-2, the leucocyte number decreased at 24 h by 30% and 50% respectively. A 50% decrease in leucocyte number was observed for 10(-5) M DON. Results were compared with haematopoietic progenitor sensitivities. Due to the differences in sensitivities between mature blood cells and haematopoietic progenitors, haematological problems associated with trichothecene intoxication could be attributed to haematopoiesis inhibition.