Effect of thermal conditioning during embryonic development on aspects of physiological responses of broilers to heat stress

The purpose of the present study was to investigate the effect of thermal conditioning, (through exposure to heat stress), during pre-hatch development on some physiological responses of post-hatch broilers to a post-natal heat stress challenge. Exposure to heat stress at this stage, we hope, may possibly induce epigenetic heat adaptation. Incubating eggs were exposed to temperature of 39.0degreesC for 2 h from Day 13 to 17 of incubation. At 33, 35, 37, 39, 41 and 43 d of age, the broilers hatched from these eggs were housed individually in open-circuit respiration cells. The climatic chambers were set to 22degreesC and increased to 30degreesC for 4 h. O-2 consumption and CO2 production of each chicken was monitored continuously in order to calculate the heat production. Blood samples were obtained before and during the 4 h heat stress. Thermal conditioning during incubation did not affect the plasma T-4, corticosterone, glucose, uric acid and CK concentrations. Temperature challenge, decreased plasma T-3 of broilers of both groups but the decrease was greater in pre-conditioned broilers compared with controls. A similar trend was observed for triglycerides. These changes did not affect total heat production. Since decreased T3 and triglyceride levels are part of the mechanisms for thermoregulation, these suggest that thermal conditioning during incubation can improve the broiler chicken capability for thermotolerance at later post-hatch age. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Triple-aspect monism: Physiological, mental unconscious and conscious aspects of brain activity

Brain activity contains three fundamental aspects: (a) The physiological aspect, covering all kinds of processes that involve matter and/or energy; (b) the mental unconscious aspect, consisting of dynamical patterns (i.e., frequency, amplitude and phase-modulated waves) embodied in neural activity. These patterns are variously operated (transmitted, stored, combined, matched, amplified, erased, etc), forming cognitive and emotional unconscious processes and (c) the mental conscious aspect, consisting of feelings experienced in the first-person perspective and cognitive functions grounded in feelings, as memory formation, selection of the focus of attention, voluntary behavior, aesthetical appraisal and ethical judgment. Triple-aspect monism (TAM) is a philosophical theory that provides a model of the relation of the three aspects. Spatially distributed neuronal dendritic potentials generate amplitude-modulated waveforms transmitted to the extracellular medium and adjacent astrocytes, prompting the formation of large waves in the astrocyte network, which are claimed to both integrate distributed information and instantiate feelings. According to the valence of the feeling, the large wave feeds back on neuronal synapses, modulating (reinforcing or depressing) cognitive and behavioral functions.

Salt stress responses in pear and quince: physiological and molecular aspects

The productivity of agricultural crops is seriously limited by salinity. This problem is rapidly increasing, particularly in irrigated lands. Like almost all the fruit tree species, Pyrus communis is generally considered a salt sensitive species, but only little information is available on its behavior under saline conditions. Previous studies, carried out in the Department of Fruit Tree and Woody Plant Science (University of Bologna), focused their attention on pear and quince salt stress responses to understand which rootstock would be the most suitable for pear in order to tolerate a salt stress condition. It has been reported that pear and quince have different ability in the uptake, translocation and accumulation of chloride (Cl-) and sodium (Na+) ions, when plants were irrigated for one season with saline water (5 dS/m). The aim of the present work was to deepen these aspects and investigate salt stress responses in pear and quince. Two different experiments have been performed: a “short-term” trial in a growth chamber and a “long-term” experiment in the open field. In the short-term experiment, three different genotypes usually adopted as pear rootstocks (MC, BA29 and Farold®40) and the pear variety Abbé Fétel own rooted have been compared under salt stress conditions. The trial was performed in a hydroponic culture system, applying a 90 mM NaCl stress to half of the plants, after five weeks of normal growth in Hoagland’s solution. During the three-weeks of salt stress treatment, physiological, mineral and molecular analyses were performed in order to monitor, for each genotype, the development of the salt stress responses in comparison with the corresponding “unstressed” plants. Farold®40 and Abbé Fétel own rooted showed the onset of leaf necrosis, due to salt toxicity, one week before quinces. Moreover, quinces displayed a significant delay in premature senescence of old leaves, while pears emerged for their ability to regenerate new leaves from apparently dead foliage with the salt stress still running. Physiological measurements, such as shoots length, chlorophyll (Chl) content, and photosynthesis, have been carried out and revealed that pears exhibited a significant reduction in water content and a wilting aspect, while for quinces a decrease in Chl content and a growth slowdown were observed. At the end of the trial, all plants were collected and organs separated for dry weight estimation and mineral analyses (Cu, Fe, Mn, Zn Mg, Ca, K, Na and Cl). Mineral contents have been affected by salinity; same macro/micro nutrients were altered in some organs or relocated within the plant. This plant response could have partially contributed to face the salt stress. Leaves and roots have been harvested for molecular analyses at four different times during stress conditions. Molecular analyses consisted of the gene expression study of three main ion transporters, well known in Arabidopsis thaliana as salt-tolerance determinants in the “SOS” pathway: NHX1 (tonoplast Na+/H+ antiporter), SOS1 (plasmalemma Na+/H+ antiporter) and HKT1 (K+ high-affinity and Na+ low-affinity transporter). These studies showed that two quince rootstocks adopted different responsive mechanisms to NaCl stress. BA29 increased its Na+ sequestration activity into leaf vacuoles, while MC enhanced temporarily the same ability, but in roots. Farold®40, instead, exhibited increases in SOS1 and HKT1 expression mainly at leaf level in the attempt to retrieve Na+ from xylem, while Abbé Fétel differently altered the expression of these genes in roots. Finally, each genotype showed a peculiar response to salt stress that was the sum of its ability in Na+ exclusion, osmotic tolerance and tissue tolerance. In the long-term experiment, potted trees of the pear variety Abbé Fétel grafted on different rootstocks (MC, BA29 and Farold®40), or own rooted and also rootstocks only were subjected to a salt stress through saline water irrigation with an electrical conductivity of 5 dS/m for two years. The purposes of this study were to evaluate salinity effects on physiological (shoot length, number of buds, photosynthesis, etc.) and yield parameters of cultivar Abbé Fétel in the different combinations and to determine the salt amount that pear is able to tolerate over the years. With this work, we confirmed the previous hypothesis that pear, despite being classified as a salt-sensitive fruit tree, can be cultivated for two years under saline water irrigation, without showing any salt toxicity symptoms or severe drawbacks on plant development and production. Among different combinations, Abbé Fétel grafted on MC resulted interesting for its peculiar behaviors under salt stress conditions. In the near future, further investigations on physiological and molecular aspects will be necessary to enrich and broaden the knowledge of salt stress responses in pear.

Jasmonates and abscisic acid influence fruit ripening and plant water use: practical, physiological and morphological aspects

The aim of the present thesis was to better understand the physiological role of the phytohormones jasmonates (JAs) and abscisic acid (ABA) during fruit ripening in prospect of a possible field application of JAs and ABA to improve fruit yield and quality. In particular, the effects of exogenous application of these substances at different fruit developmental stages and under different experimental conditions were evaluated. Some aspects of the water relations upon ABA treatment were also analysed. Three fruit species, peach (Prunus persica L. Batsch), golden (Actinidia chinensis) and green kiwifruit (Actinidia deliciosa), and several of their cvs, were used for the trials. Different experimental models were adopted: fruits in planta, detached fruit, detached branches with fruit, girdled branches and micropropagated plants. The work was structured into four sets of experiments as follows: (i) Pre-harvest methyl jasmonate (MJ) application was performed at S3/S4 transition under field conditions in Redhaven peach; ethylene production, ripening index, fruit quality and shelf-life were assessed showing that MJ-treated fruit were firmer and thus less ripe than controls as confirmed by the Index of Absorbance Difference (IAD), but exhibited a shorter shelf-life due to an increase in ethylene production. Moreover, the time course of the expression of ethylene-, auxin- and other ripening-related genes was determined. Ripening-related ACO1 and ACS1 transcript accumulation was inhibited though transiently by MJ, and gene expression of the ethylene receptor ETR2 and of the ethylene-related transcription factor ERF2 was also altered. The time course of the expression of several auxin-related genes was strongly affected by MJ suggesting an increase in auxin biosynthesis, altered auxin conjugation and release as well as perception and transport; the need for a correct ethylene/auxin balance during ripening was confirmed. (ii) Pre- and post-harvest ABA applications were carried out under field conditions in Flaminia and O’Henry peach and Stark Red Gold nectarine fruit; ethylene production, ripening index, fruit quality and shelf-life were assessed. Results show that pre-harvest ABA applications increase fruit size and skin color intensity. Also post-harvest ABA treatments alter ripening-related parameters; in particular, while ethylene production is impaired in ABA-treated fruit soluble solids concentration (SSC) is enhanced. Following field ABA applications stem water potential was modified since ABA-treated peach trees retain more water. (iii) Pre- and post-harvest ABA and PDJ treatments were carried out in both kiwifruit species under field conditions at different fruit developmental stages and in post-harvest. Ripening index, fruit quality, plant transpiration, photosynthesis and stomatal conductance were assessed. Pre-harvest treatments enhance SSC in the two cvs and flesh color development in golden kiwifruit. Post-harvest applications of either ABA or ABA plus PDJ lead to increased SSC. In addition, ABA reduces gas exchanges in A. deliciosa. (iv) Spray, drench and dipping ABA treatments were performed in micropropagated peach plants and in peach and nectarine detached branches; plant water use and transpiration, biomass production and fruit dehydration were determined. In both plants and branches ABA significantly reduces water use and fruit dehydration. No negative effects on biomass production were detected. The present information, mainly arising from plant growth regulator application in a field environment, where plants have to cope with multiple biotic and abiotic stresses, may implement the perspectives for the use of these substances in the control of fruit ripening.

Physiological and Biochemical Aspects of Iron Nutrition in Grapevine

The objective of this thesis was to study the response mechanisms of grapevine to Fe-deficiency and to potential Fe chlorosis prevention strategies. The results show that the presence of bicarbonate in the nutrient solution shifted the activity of PEPC and TCA cycle enzymes and the accumulation/translocation of organic acids in roots of Fe-deprived plants. The rootstock 140 Ruggeri displayed a typical behavior of calcicole plants under bicarbonate stress. The Fe chlorosis susceptible rootstock 101-14 reacted to a prolonged Fe-deficiency reducing the root activity of PEPC and MDH. Noteworthy, it accumulates high levels of citric acid in roots, indicating a low capacity to utilizing, transporting and/or exudating organic acids into the rhizosfere. In contrast, 110 Richter rootstock is capable to maintain an active metabolism of organic acids in roots, accumulating them to a lesser extent than 101-14. Similarly to 101-14, SO4 genotype displays a strong decrease of mechanisms associated to Fe chlorosis tolerance (PEPC and MDH enzymes). Nevertheless it is able to avoid excessive accumulation of citric acid in roots, similar as 110 Richter rootstock. Intercropping with Festuca rubra increased leaf chlorophyll content and net photosynthesis. In addition, intercropping reduces the activity of PEPC in roots, similary to Fe-chelate supply. Applications of NH4+ with nitrification inhibitor prevents efficiently Fe-deficiency, increases chlorophyll content, and induces similar root biochemical responses as Fe-EDDHA. Without the addition of nitrification inhibitors, the effectiveness of NH4+ supply on Fe chlorosis prevention resulted significantly lower. The aspects intertwined in this investigation highlight the complexity of Fe physiology and the fine metabolic tuning of grapevine genotypes to Fe availability and soil-related environmental factors. The experimental evidences reveal the need to carry out future researches on Fe nutrition maintaining a continous flow of knowledge between theoretical and agronomical perspectives for fully supporting the efforts devoted to convert science into practice.

Physiological and structural aspects of fruit and vegetable mild processing

Over the past years fruit and vegetable industry has become interested in the application of both osmotic dehydration and vacuum impregnation as mild technologies because of their low temperature and energy requirements. Osmotic dehydration is a partial dewatering process by immersion of cellular tissue in hypertonic solution. The diffusion of water from the vegetable tissue to the solution is usually accompanied by the simultaneous solutes counter-diffusion into the tissue. Vacuum impregnation is a unit operation in which porous products are immersed in a solution and subjected to a two-steps pressure change. The first step (vacuum increase) consists of the reduction of the pressure in a solid-liquid system and the gas in the product pores is expanded, partially flowing out. When the atmospheric pressure is restored (second step), the residual gas in the pores compresses and the external liquid flows into the pores. This unit operation allows introducing specific solutes in the tissue, e.g. antioxidants, pH regulators, preservatives, cryoprotectancts. Fruit and vegetable interact dynamically with the environment and the present study attempts to enhance our understanding on the structural, physico-chemical and metabolic changes of plant tissues upon the application of technological processes (osmotic dehydration and vacuum impregnation), by following a multianalytical approach. Macro (low-frequency nuclear magnetic resonance), micro (light microscopy) and ultrastructural (transmission electron microscopy) measurements combined with textural and differential scanning calorimetry analysis allowed evaluating the effects of individual osmotic dehydration or vacuum impregnation processes on (i) the interaction between air and liquid in real plant tissues, (ii) the plant tissue water state and (iii) the cell compartments. Isothermal calorimetry, respiration and photosynthesis determinations led to investigate the metabolic changes upon the application of osmotic dehydration or vacuum impregnation. The proposed multianalytical approach should enable both better designs of processing technologies and estimations of their effects on tissue.

The urea transporter family (SLC14): physiological, pathological and structural aspects

Urea transporters (UTs) belonging to the solute carrier 14 (SLC14) family comprise two genes with a total of eight isoforms in mammals, UT-A1 to -A6 encoded by SLC14A2 and UT-B1 to -B2 encoded by SLC14A1. Recent efforts have been directed toward understanding the molecular and cellular mechanisms involved in the regulation of UTs using transgenic mouse models and heterologous expression systems, leading to important new insights. Urea uptake by UT-A1 and UT-A3 in the kidney inner medullary collecting duct and by UT-B1 in the descending vasa recta for the countercurrent exchange system are chiefly responsible for medullary urea accumulation in the urinary concentration process. Vasopressin, an antidiuretic hormone, regulates UT-A isoforms via the phosphorylation and trafficking of the glycosylated transporters to the plasma membrane that occurs to maintain equilibrium with the exocytosis and ubiquitin-proteasome degradation pathways. UT-B isoforms are also important in several cellular functions, including urea nitrogen salvaging in the colon, nitric oxide pathway modulation in the hippocampus, and the normal cardiac conduction system. In addition, genomic linkage studies have revealed potential additional roles for SLC14A1 and SLC14A2 in hypertension and bladder carcinogenesis. The precise role of UT-A2 and presence of the urea recycling pathway in normal kidney are issues to be further explored. This review provides an update of these advances and their implications for our current understanding of the SLC14 UTs.

Body and will; being an essay concerning will in its metaphysical, physiological, and pathological aspects,

Mode of access: Internet.

Temporal aspects of the VO2 response at the power output associated with VO2peak in well trained cyclists: Implications for interval training prescription

The power output achieved at peak oxygen consumption (VO2 peak) and the time this power can be maintained (i.e., Tmax) have been used in prescribing high-intensity interval training. In this context, the present study examined temporal aspects of the VO2 response to exercise at the cycling power that output well trained cyclists achieve their VO2 peak (i.e., Pmax). Following a progressive exercise test to determine VO2 peak, 43 well trained male cyclists (M age = 25 years, SD = 6; M mass = 75 kg SD = 7; M VO2 peak = 64.8 ml(.)kg(1.)min(-1), SD = 5.2) performed two Tmax tests 1 week apart.1. Values expressed for each participant are means and standard deviations of these two tests. Participants achieved a mean VO2 peak during the Tmax test after 176 s (SD = 40; = 74% of Tmax, SD = 12) and maintained it for 66 s (SD = 39; M = 26% of Tmax, SD = 12). Additionally they obtained mean 95 % of VO2 peak after 147 s (SD = 31; M = 62 % of Tmax, SD = 8) and maintained it for 95 s (SD = 38; M = 38 % of Tmax, SD = 8). These results suggest that 60-70% of Tmax is an appropriate exercise duration for a population of well trained cyclists to attain VO2 peak during exercise at Pmax. However due to intraparticipant variability in the temporal aspects of the VO2 response to exercise at Pmax, future research is needed to examine whether individual high-intensity interval training programs for well trained endurance athletes might best be prescribed according to an athlete's individual VO2 response to exercise at Pmax.

Overeating as a clue to weight gain: behavioural and physiological interactions in the control of food intake

It has been estimated that 25-50% of people in most affluent societies are either obese or overweight. These disorders are the result of an imbalance between calorific intake and energy expenditure over a prolonged time period. These types of disorders are among the most common health problems in industrialized societies. Addressing these issues and offering new strategies, this thorough new study draws together contributions from interdisciplinary and international group of specialists, includes recent research on genetic influences, features discussions of epidemiological studies and covers both biological and social aspects of obesity.

Physiological investigation of periosteum structure and its application in periosteum tissue engineering

Although many different materials, techniques and methods, including artificial or engineered bone substitutes, have been used to repair various bone defects, the restoration of critical-sized bone defects caused by trauma, surgery or congenital malformation is still a great challenge to orthopedic surgeons. One important fact that has been neglected in the pursuit of resolutions for large bone defect healing is that most physiological bone defect healing needs the periosteum and stripping off the periosteum may result in non-union or non-healed bone defects. Periosteum plays very important roles not only in bone development but also in bone defect healing. The purpose of this project was to construct a functional periosteum in vitro using a single stem cell source and then test its ability to aid the repair of critical-sized bone defect in animal models. This project was designed with three separate but closely-linked parts which in the end led to four independent papers. The first part of this study investigated the structural and cellular features in periostea from diaphyseal and metaphyseal bone surfaces in rats of different ages or with osteoporosis. Histological and immunohistological methods were used in this part of the study. Results revealed that the structure and cell populations in periosteum are both age-related and site-specific. The diaphyseal periosteum showed age-related degeneration, whereas the metaphyseal periosteum is more destructive in older aged rats. The periosteum from osteoporotic bones differs from normal bones both in terms of structure and cell populations. This is especially evident in the cambial layer of the metaphyseal area. Bone resorption appears to be more active in the periosteum from osteoporotic bones, whereas bone formation activity is comparable between the osteoporotic and normal bone. The dysregulation of bone resorption and formation in the periosteum may also be the effect of the interaction between various neural pathways and the cell populations residing within it. One of the most important aspects in periosteum engineering is how to introduce new blood vessels into the engineered periosteum to help form vascularized bone tissues in bone defect areas. The second part of this study was designed to investigate the possibility of differentiating bone marrow stromal cells (BMSCs) into the endothelial cells and using them to construct vascularized periosteum. The endothelial cell differentiation of BMSCs was induced in pro-angiogenic media under both normoxia and CoCl2 (hypoxia-mimicking agent)-induced hypoxia conditions. The VEGF/PEDF expression pattern, endothelial cell specific marker expression, in vitro and in vivo vascularization ability of BMSCs cultured in different situations were assessed. Results revealed that BMSCs most likely cannot be differentiated into endothelial cells through the application of pro-angiogenic growth factors or by culturing under CoCl2-induced hypoxic conditions. However, they may be involved in angiogenesis as regulators under both normoxia and hypoxia conditions. Two major angiogenesis-related growth factors, VEGF (pro-angiogenic) and PEDF (anti-angiogenic) were found to have altered their expressions in accordance with the extracellular environment. BMSCs treated with the hypoxia-mimicking agent CoCl2 expressed more VEGF and less PEDF and enhanced the vascularization of subcutaneous implants in vivo. Based on the findings of the second part, the CoCl2 pre-treated BMSCs were used to construct periosteum, and the in vivo vascularization and osteogenesis of the constructed periosteum were assessed in the third part of this project. The findings of the third part revealed that BMSCs pre-treated with CoCl2 could enhance both ectopic and orthotopic osteogenesis of BMSCs-derived osteoblasts and vascularization at the early osteogenic stage, and the endothelial cells (HUVECs), which were used as positive control, were only capable of promoting osteogenesis after four-weeks. The subcutaneous area of the mouse is most likely inappropriate for assessing new bone formation on collagen scaffolds. This study demonstrated the potential application of CoCl2 pre-treated BMSCs in the tissue engineering not only for periosteum but also bone or other vascularized tissues. In summary, the structure and cell populations in periosteum are age-related, site-specific and closely linked with bone health status. BMSCs as a stem cell source for periosteum engineering are not endothelial cell progenitors but regulators, and CoCl2-treated BMSCs expressed more VEGF and less PEDF. These CoCl2-treated BMSCs enhanced both vascularization and osteogenesis in constructed periosteum transplanted in vivo.

Effect of carbohydrate ingestion and ambient temperature on muscle fatigue development in endurance-trained male cyclists

The aim of the present study was to determine the effect of carbohydrate (CHO; sucrose) ingestion and environmental heat on the development of fatigue and the distribution of power output during a 16.1-km cycling time trial. Ten male cyclists (Vo(2max) = 61.7 +/- 5.0 ml.kg(-1).min(-1), mean +/- SD) performed four 90-min constant-pace cycling trials at 80% of second ventilatory threshold (220 +/- 12 W). Trials were conducted in temperate (18.1 +/- 0.4 degrees C) or hot (32.2 +/- 0.7 degrees C) conditions during which subjects ingested either CHO (0.96 g.kg(-1).h(-1)) or placebo (PLA) gels. All trials were followed by a 16.1-km time trial. Before and immediately after exercise, percent muscle activation was determined using superimposed electrical stimulation. Power output, integrated electromyography (iEMG) of vastus lateralis, rectal temperature, and skin temperature were recorded throughout the trial. Percent muscle activation significantly declined during the CHO and PLA trials in hot (6.0 and 6.9%, respectively) but not temperate conditions (1.9 and 2.2%, respectively). The decline in power output during the first 6 km was significantly greater during exercise in the heat. iEMG correlated significantly with power output during the CHO trials in hot and temperate conditions (r = 0.93 and 0.73; P < 0.05) but not during either PLA trial. In conclusion, cyclists tended to self-select an aggressive pacing strategy (initial high intensity) in the heat.

Effects of bovine colostrum supplementation on immune variables of highly-trained cyclists

The aim of this study was to investigate the influence of low-dose bovine colostrum protein concentrate (CPC) supplementation on selected immune variables in cyclists. Twenty-nine highly trained male road cyclists completed an initial 40-km time trial (TT(40)) and were then randomly assigned to either a supplement (n = 14, 10 g bovine CPC/day) or placebo group (n = 15, 10 g whey protein concentrate/day). After 5 wk of supplementation, the cyclists completed a second TT(40). They then completed 5 consecutive days of high-intensity training (HIT) that included a TT(40), followed by a final TT(40) in the following week. Venous blood and saliva samples were collected immediately before and after each TT(40), and upper respiratory illness symptoms were recorded over the experimental period. Compared with the placebo group, bovine CPC supplementation significantly increased preexercise serum soluble TNF receptor 1 during the HIT period (bovine CPC = 882 +/- 233 pg/ml, placebo = 468 +/- 139 pg/ml; P = 0.039). Supplementation also suppressed the postexercise decrease in cytotoxic/suppressor T cells during the HIT period (bovine CPC = -1.0 +/- 2.7%, placebo = -9.2 +/- 2.8%; P = 0.017) and during the following week (bovine CPC = 1.4 +/- 2.9%, placebo = -8.2 +/- 2.8%; P = 0.004). Bovine CPC supplementation prevented a postexercise decrease in serum IgG(2) concentration at the end of the HIT period (bovine CPC = 4.8 +/- 6.8%, P = 0.88; placebo = -9.7 +/- 6.9%, P = 0.013). There was a trend toward reduced incidence of upper respiratory illness symptoms in the bovine CPC group (P = 0.055). In summary, low-dose bovine CPC supplementation modulates immune parameters during normal training and after an acute period of intense exercise, which may have contributed to the trend toward reduced upper respiratory illness in the bovine CPC group.

Carcinogenicity and genotoxicity of ethylene oxide : new aspects and recent advances

Long-term inhalation studies in rodents have presented unequivocal evidence of experimental carcinogenicity of ethylene oxide, based on the formation of malignant tumors at multiple sites. However, despite a considerable body of epidemiological data only limited evidence has been obtained of its carcinogenicity in humans. Ethylene oxide is not only an important exogenous toxicant, but it is also formed from ethylene as a biological precursor. Ethylene is a normal body constituent; its endogenous formation is evidenced by exhalation in rats and in humans. Consequently, ethylene oxide must also be regarded as a physiological compound. The most abundant DNA adduct of ethylene oxide is 7-(2-hydroxyethyl)guanine (HOEtG). Open questions are the nature and role of tissue-specific factors in ethylene oxide carcinogenesis and the physiological and quantitative role of DNA repair mechanisms. The detection of remarkable individual differences in the susceptibility of humans has promoted research into genetic factors that influence the metabolism of ethylene oxide. With this background it appears that current PBPK models for trans-species extrapolation of ethylene oxide toxicity need to be refined further. For a cancer risk assessment at low levels of DNA damage, exposure-related adducts must be discussed in relation to background DNA damage as well as to inter- and intraindividual variability. In rats, subacute ethylene oxide exposures on the order of 1 ppm (1.83 mg/m3) cause DNA adduct levels (HOEtG) of the same magnitude as produced by endogenous ethylene oxide. Based on very recent studies the endogenous background levels of HOEtG in DNA of humans are comparable to those that are produced in rodents by repetitive exogenous ethylene oxide exposures of about 10 ppm (18.3 mg/m3). Experimentally, ethylene oxide has revealed only weak mutagenic effects in vivo, which are confined to higher doses. It has been concluded that long-term human occupational exposure to low airborne concentrations to ethylene oxide, at or below current occupational exposure limits of 1 ppm (1.83 mg/m3), would not produce unacceptable increased genotoxic risks. However, critical questions remain that need further discussions relating to the coherence of animal and human data of experimental data in vitro vs. in vivo and to species-specific dynamics of DNA lesions.