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1.
《Nanotoxicology》2013,7(5):974-988
AbstractSince nanomaterials are a heterogeneous group of substances used in various applications, risk assessment needs to be done on a case-by-case basis. Here the authors assess the risk (hazard and exposure) of a glass cleaner with synthetic amorphous silicon dioxide (SAS) nanoparticles during production and consumer use (spray application). As the colloidal material used is similar to previously investigated SAS, the hazard profile was considered to be comparable. Overall, SAS has a low toxicity. Worker exposure was analysed to be well controlled. The particle size distribution indicated that the aerosol droplets were in a size range not expected to reach the alveoli. Predictive modelling was used to approximate external exposure concentrations. Consumer and environmental exposure were estimated conservatively and were not of concern. It was concluded based on the available weight-of-evidence that the production and application of the glass cleaner is safe for humans and the environment under intended use conditions. 相似文献
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《Nanotoxicology》2013,7(8):1087-1101
AbstractTitanium dioxide (TiO2) is widely used in pharmaceuticals preparations, cosmetics, and as a food additive (E171). It contains microparticles and a fraction of nanoparticles (NPs) which can be absorbed systemically by humans after ingestion. Increasing concern has been aroused about the impact of oral exposure to TiO2 NPs from dietary and non-dietary sources on human health. In spite of several toxicological studies conducted in recent years, a solid risk assessment of oral exposure to E171 has not been satisfactorily achieved. We investigated whether repeated oral administration of E171 to mice at a dose level (5?mg/kg body weight for 3?days/week for 3?weeks) comparable to estimated human dietary exposure, results in TiO2 deposition in the digestive system and internal organs, and in molecular and cellular alterations associated with an inflammatory response. To reproduce the first phase of digestion, a new administration approach involving the dripping of the E171 suspension into the mouth of mice was applied. Significant accumulation of titanium was observed in the liver and intestine of E171-fed mice; in the latter a threefold increase in the number of TiO2 particles was also measured. Titanium accumulation in liver was associated with necroinflammatory foci containing tissue monocytes/macrophages. Three days after the last dose, increased superoxide production and inflammation were observed in the stomach and intestine. Overall, the present study indicates that the risk for human health associated with dietary exposure to E171 needs to be carefully considered. 相似文献
3.
Minne B. Heringa Liesbeth Geraets Jan C. H. van Eijkeren Rob J. Vandebriel Wim H. de Jong 《Nanotoxicology》2016,10(10):1515-1525
Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (<100?nm). It is applied in food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO2 NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO2 NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO2, particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO2 (NPs) in animals are recommended to refine this assessment. 相似文献
4.
This study aimed to conduct an integrated and probabilistic risk assessment of gold nanoparticles (AuNPs) based on recently published in vitro and in vivo toxicity studies coupled to a physiologically based pharmacokinetic (PBPK) model. Dose–response relationships were characterized based on cell viability assays in various human cell types. A previously well-validated human PBPK model for AuNPs was applied to quantify internal concentrations in liver, kidney, skin, and venous plasma. By applying a Bayesian-based probabilistic risk assessment approach incorporating Monte Carlo simulation, probable human cell death fractions were characterized. Additionally, we implemented in vitro to in vivo and animal-to-human extrapolation approaches to independently estimate external exposure levels of AuNPs that cause minimal toxicity. Our results suggest that under the highest dosing level employed in existing animal studies (worst-case scenario), AuNPs coated with branched polyethylenimine (BPEI) would likely induce ~90–100% cellular death, implying high cytotoxicity compared to <10% cell death induced by low-to-medium animal dosing levels, which are commonly used in animal studies. The estimated human equivalent doses associated with 5% cell death in liver and kidney were around 1 and 3?mg/kg, respectively. Based on points of departure reported in animal studies, the human equivalent dose estimates associated with gene expression changes and tissue cell apoptosis in liver were 0.005 and 0.5?mg/kg, respectively. Our analyzes provide insights into safety evaluation, risk prediction, and point of departure estimation of AuNP exposure for humans and illustrate an approach that could be applied to other NPs when sufficient data are available. 相似文献
5.
目的 测定市售灵芝孢子粉中铅、镉、砷、汞、铜、铬、镍7种重金属元素的残留量并评估其膳食暴露的健康风险。方法 收集市售灵芝孢子粉(包含中药饮片、保健食品、食品和农产品等不同产品类型)40批次,对7种重金属元素进行检测,采用点评估方法对灵芝孢子粉中7种重金属元素的膳食暴露量进行评估。结果 40批灵芝孢子粉中7种重金属元素检出率均为100%,有8批样品重金属元素超出拟定的限度。重金属元素膳食暴露评估显示消费者食用灵芝孢子粉摄入铬的量存在一定的膳食暴露健康风险。结论 灵芝孢子粉中铅、镉、砷、汞、铜、镍6种重金属元素膳食暴露低于暂定可耐受摄入量,对人体健康产生危害的风险可接受;铬元素膳食暴露的最大值和第95百分位数(P95)值超过暂定可耐受摄入量,存在一定的健康风险。 相似文献
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8.
Ana Luísa Vasconcelos Maria João Silva 《Journal of toxicology and environmental health. Part A》2019,82(9):526-536
ABSTRACTPlasticizers are currently present in many consumer products, particularly food packaging, children’s toys, and medical devices. There are concerns regarding potential leaching to environment or food, thus increasing the risk of human exposure by inhalation, ingestion and/or dermal absorption potentially leading to adverse health consequences. Hexamoll diisononyl cyclohexane-1,2-dicarboxylate (Hexamoll® DINCH®), a non-phthalate plasticizer, has been used as a safer alternative to hazardous phthalates. In contrast to phthalates, evidence indicates that DINCH did not produce endocrine disruption, reproductive dysfunctions, genotoxicity or mutagenicity. However, there are limited data available regarding safety assessment, especially with respect to genotoxicity in human cells. The aim of this study was to assess DINCH cytotoxic and genotoxic effects in human liver and kidney cell lines following several exposure periods. For this purpose, the MTT cell viability, micronucleus, conventional and formamidopyrimidine DNA glycosylase (FPG)-modified comet assays were employed to detect cell death and genotoxicity, respectively. Data demonstrated that DINCH induced cytotoxicity in kidney cells exposed for 48hr, but not in liver cells. No marked chromosomal damage was noted after short-term or longer following treatment of both cell lines. However, DINCH produced oxidative DNA damage in liver cells exposed for 3 h, which decreased after a more prolonged incubation period. The occurrence of oxidative lesions, even transiently, indicates that mutation fixation may occur leading to adverse effects in liver. Therefore, these findings suggest that DINCH may be hazardous to humans and that further investigation is necessary to warrant its safety. 相似文献
9.
Len Ritter Keith Solomon Paul Sibley Ken Hall Patricia Keen Gevan Mattu Beth Linton 《Journal of toxicology and environmental health. Part A》2002,65(1):1-142
On a global scale, pathogenic contamination of drinking water poses the most significant health risk to humans, and there have been countless numbers of disease outbreaks and poisonings throughout history resulting from exposure to untreated or poorly treated drinking water. However, significant risks to human health may also result from exposure to nonpathogenic, toxic contaminants that are often globally ubiquitous in waters from which drinking water is derived. With this latter point in mind, the objective of this commission paper is to discuss the primary sources of toxic contaminants in surface waters and groundwater, the pathways through which they move in aquatic environments, factors that affect their concentration and structure along the many transport flow paths, and the relative risks that these contaminants pose to human and environmental health. In assessing the relative risk of toxic contaminants in drinking water to humans, we have organized our discussion to follow the classical risk assessment paradigm, with emphasis placed on risk characterization. In doing so, we have focused predominantly on toxic contaminants that have had a demonstrated or potential effect on human health via exposure through drinking water. In the risk assessment process, understanding the sources and pathways for contaminants in the environment is a crucial step in addressing (and reducing) uncertainty associated with estimating the likelihood of exposure to contaminants in drinking water. More importantly, understanding the sources and pathways of contaminants strengthens our ability to quantify effects through accurate measurement and testing, or to predict the likelihood of effects based on empirical models. Understanding the sources, fate, and concentrations of chemicals in water, in conjunction with assessment of effects, not only forms the basis of risk characterization, but also provides critical information required to render decisions regarding regulatory initiatives, remediation, monitoring, and management. Our discussion is divided into two primary themes. First we discuss the major sources of contaminants from anthropogenic activities to aquatic surface and groundwater and the pathways along which these contaminants move to become incorporated into drinking water supplies. Second, we assess the health significance of the contaminants reported and identify uncertainties associated with exposures and potential effects. Loading of contaminants to surface waters, groundwater, sediments, and drinking water occurs via two primary routes: (1) point-source pollution and (2) non-point-source pollution. Point-source pollution originates from discrete sources whose inputs into aquatic systems can often be defined in a spatially explicit manner. Examples of point-source pollution include industrial effluents (pulp and paper mills, steel plants, food processing plants), municipal sewage treatment plants and combined sewage-storm-water overflows, resource extraction (mining), and land disposal sites (landfill sites, industrial impoundments). Non-point-source pollution, in contrast, originates from poorly defined, diffuse sources that typically occur over broad geographical scales. Examples of non-point-source pollution include agricultural runoff (pesticides, pathogens, and fertilizers), storm-water and urban runoff, and atmospheric deposition (wet and dry deposition of persistent organic pollutants such as polychlorinated biphenyls [PCBs] and mercury). Within each source, we identify the most important contaminants that have either been demonstrated to pose significant risks to human health and/or aquatic ecosystem integrity, or which are suspected of posing such risks. Examples include nutrients, metals, pesticides, persistent organic pollutants (POPs), chlorination by-products, and pharmaceuticals. Due to the significant number of toxic contaminants in the environment, we have necessarily restricted our discussion to those chemicals that pose risks to human health via exposure through drinking water. A comprehensive and judicious consideration of the full range of contaminants that occur in surface waters, sediments, and drinking water would be a large undertaking and clearly beyond the scope of this article. However, where available, we have provided references to relevant literature to assist the reader in undertaking a detailed investigation of their own. The information collected on specific chemicals within major contaminant classes was used to determine their relative risk using the hazard quotient (HQ) approach. Hazard quotients are the most widely used method of assessing risk in which the exposure concentration of a stressor, either measured or estimated, is compared to an effect concentration (e.g., no-observed-effect concentration or NOEC). A key goal of this assessment was to develop a perspective on the relative risks associated with toxic contaminants that occur in drinking water. Data used in this assessment were collected from literature sources and from the Drinking Water Surveillance Program (DWSP) of Ontario. For many common contaminants, there was insufficient environmental exposure (concentration) information in Ontario drinking water and groundwater. Hence, our assessment was limited to specific compounds within major contaminant classes including metals, disinfection by-products, pesticides, and nitrates. For each contaminant, the HQ was estimated by expressing the maximum concentration recorded in drinking water as a function of the water quality guideline for that compound. There are limitations to using the hazard quotient approach of risk characterization. For example, HQs frequently make use of worst-case data and are thus designed to be protective of almost all possible situations that may occur. However, reduction of the probability of a type II error (false negative) through the use of very conservative application factors and assumptions can lead to the implementation of expensive measures of mitigation for stressors that may pose little threat to humans or the environment. It is important to realize that our goal was not to conduct a comprehensive, in-depth assessment of risk for each chemical; more comprehensive assessments of managing risks associated with drinking water are addressed in a separate issue paper by Krewski et al. (2001a). Rather, our goal was to provide the reader with an indication of the relative risk of major contaminant classes as a basis for understanding the risks associated with the myriad forms of toxic pollutants in aquatic systems and drinking water. For most compounds, the estimated HQs were < 1. This indicates that there is little risk associated with exposure from drinking water to the compounds tested. There were some exceptions. For example, nitrates were found to commonly yield HQ values well above 1 in- many rural areas. Further, lead, total trihalomethanes, and trichloroacetic acid yielded HQs > 1 in some treated distribution waters (water distributed to households). These latter compounds were further assessed using a probabilistic approach; these assessments indicated that the maximum allowable concentrations (MAC) or interim MACs for the respective compounds were exceeded <5% of the time. In other words, the probability of finding these compounds in drinking water at levels that pose risk to humans through ingestion of drinking water is low. Our review has been carried out in accordance with the conventional principles of risk assessment. Application of the risk assessment paradigm requires rigorous data on both exposure and toxicity in order to adequately characterize potential risks of contaminants to human health and ecological integrity. Weakness rendered by poor data, or lack of data, in either the exposure or effects stages of the risk assessment process significantly reduces the confidence that can be placed in the overall risk assessment. Overall, while our review suggested selected instances of potential risks to human health from exposure to contaminants in drinking water, we also noted a distinct paucity of information on exposure levels for many contaminants in this matrix. We suggest that this represents a significant limitation to conducting sound risk assessments and introduces considerable uncertainty with respect to the management of water quality. In this context, future research must place greater emphasis on targeted monitoring and assessment of specific contaminants (e.g., pharmaceuticals) in drinking water for which there is currently little information. This could be conducted using a tiered risk approach, beginning with, for example, a hazard quotient assessment. Potentially problematic compounds identified in these preliminary assessments would then be subjected to more comprehensive risk assessments using probabilistic methods, if sufficient data exist to do so. On this latter point, adequate assessment of potential risks for many contaminants in drinking water is currently limited by a paucity of toxicological information. Generating this important information is a critical research need and would reduce the uncertainty associated with conducting risk assessments. 相似文献
10.
P van den Brandt L Voorrips I Hertz-Picciotto D Shuker H Boeing G Speijers C Guittard J Kleiner M Knowles A Wolk A Goldbohm 《Food and chemical toxicology》2002,40(2-3):387-424
Epidemiologic studies directly contribute data on risk (or benefit) in humans as the investigated species, and in the full food intake range normally encountered by humans. This paper starts with introducing the epidemiologic approach, followed by a discussion of perceived differences between toxicological and epidemiologic risk assessment. Areas of contribution of epidemiology to the risk assessment process are identified, and ideas for tailoring epidemiologic studies to the risk assessment procedures are suggested, dealing with data collection, analyses and reporting of both existing and new epidemiologic studies. The dietary habits and subsequent disease occurrence of over three million people are currently under observation worldwide in cohort studies, offering great potential for use in risk assessment. The use of biomarkers and data on genetic susceptibility are discussed. The paper describes a scheme to classify epidemiologic studies for use in risk assessment, and deals with combining evidence from multiple studies. Using a matrix approach, the potential contribution to each of the steps in the risk assessment process is evaluated for categories of food substances. The contribution to risk assessment of specific food substances depends on the quality of the exposure information. Strengths and weaknesses are summarized. It is concluded that epidemiology can contribute significantly to hazard identification, hazard characterisation and exposure assessment. 相似文献
11.
《Critical reviews in toxicology》2013,43(5):367-387
AbstractCobalt (Co) can stimulate erythropoietin production in individuals at doses exceeding 25 mg CoCl2/day. Co has also been shown to exert effects on the thyroid gland, heart and nervous system at sufficient doses. The biological activity of Co is dictated by the concentration of free (unbound) ionic Co2+. Blood concentrations, as well as, urinary excretion rates of Co are reliable biomarkers for systemic Co exposure. A recent series of human volunteer Co-supplement studies simultaneously measured Co blood and urine concentrations, as well as, Co speciation in serum, and a number of biochemical and clinical parameters. It was found in these studies that peak Co whole blood concentration as high as 117 μg/L were not associated with changes in hematological parameters such as increased red blood cell (RBC) count, hemoglobin (Hgb) or hematocrit (Hct) levels, nor with changes in cardiac, neurological or, thyroid function. Using a Co biokinetic model, the estimated Co systemic tissue concentrations (e.g., liver, kidney, and heart) following 90-days of Co-dietary supplementation with ~1 mg Co/day were found to be similar to estimated tissue concentrations in implant patients after 10 years of exposure at continuous steady state Co blood concentration of ~10 μg/L. This study is the first to present modeled Co tissue concentrations at various doses following sub-chronic and chronic exposure. The modeled steady state tissue Co concentrations in combination with the data on adverse health effects in humans should help in the characterization of potential hazards associated with increased blood Co concentrations due to exposure to dietary supplements or cobalt-chromium (Co-Cr) containing implants. 相似文献
12.
Comparative pharmacokinetics of perfluorooctanesulfonate (PFOS) in rats, mice, and monkeys 总被引:1,自引:0,他引:1
Chang SC Noker PE Gorman GS Gibson SJ Hart JA Ehresman DJ Butenhoff JL 《Reproductive toxicology (Elmsford, N.Y.)》2012,33(4):428-440
Perfluorooctanesulfonate (PFOS) has been found in biological samples in wildlife and humans. The geometric mean half-life of serum elimination of PFOS in humans has been estimated to be 4.8 years (95% CI, 4.0–5.8). A series of studies was undertaken to establish pharmacokinetic parameters for PFOS in rats, mice, and monkeys after single oral and/or IV administration of K+PFOS. Animals were followed for up to 23 weeks, and pharmacokinetic parameters were determined by WinNonlin® software. Rats and mice appeared to be more effective at eliminating PFOS than monkeys. The serum elimination half-lives in the rodent species were on the order of 1–2 months; whereas, in monkeys, the serum elimination half lives approximated 4 months. Collectively, these studies provide valuable insight for human health risk assessment regarding the potential for accumulation of body burden in humans on repeated exposure to PFOS and PFOS-generating materials. 相似文献
13.
Medicinal herbs have been increasingly used for therapeutic purposes against a diverse range of human diseases worldwide. Moreover, the health benefits of spices have been extensively recognized in recent studies. However, inevitable contaminants, including mycotoxins, in medicinal herbs and spices can cause serious problems for humans in spite of their health benefits. Along with the different nation-based occurrences of mycotoxins, the ultimate exposure and toxicities can be diversely influenced by the endogenous food components in different commodities of the medicinal herbs and spices. The phytochemicals in these food stuffs can influence mold growth, mycotoxin production and biological action of the mycotoxins in exposed crops, as well as in animal and human bodies. The present review focuses on the occurrence of mycotoxins in medicinal herbs and spices and the biological interaction between mold, mycotoxin and herbal components. These networks will provide insights into the methods of mycotoxin reduction and toxicological risk assessment of mycotoxin-contaminated medicinal food components in the environment and biological organisms. 相似文献
14.
Masanao Yamashita Hiroshi Suemizu Norie Murayama Sayako Nishiyama Makiko Shimizu Hiroshi Yamazaki 《Regulatory toxicology and pharmacology : RTP》2014
To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats. 相似文献
15.
Mielke H Abraham K Götz M Vieth B Lampen A Luch A Gundert-Remy U 《Toxicology letters》2011,202(2):100-110
Coumarin (1,2-benzopyrone) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in humans by simulating both routes of exposure. The concentration-time profile in liver revealed a higher peak concentration (Cmax-hep) for the oral when compared to the dermal route. The area under the concentration-time curve in the liver (AUChep) was found the same for both routes if the same extent of absorption is assumed. Dose response information from published rat studies were used to identify the metric relevant for liver toxicity. Liver exposure levels resulting from doses and durations as outlined in the studies were simulated in a rat model. We obtained 31 data pairs of Cmax-hep and AUChep. Liver toxicity was observed at doses which resulted in simulated Cmax-hep values exceeding a certain liver concentration whereas we could not identify a clear cut off value of AUChep. Our findings support the notion that liver toxicity of coumarin in rats is related to Cmax-hep rather than to AUChep. If these findings can be transferred to the situation in humans, the result demonstrates that route specific differences in organ peak concentrations have to be considered when performing route-to-route extrapolation. 相似文献
16.
For several decades, food-grade synthetic amorphous silica (SAS) have been used as a technological additive to reduce caking of food powders. Human exposure is thus inevitable and safety concerns are taken seriously. The toxicity of silica in general and SAS in particular has been studied extensively. Overall, there is little evidence that food-grade SAS pose any health risks to humans. However, from the available data it was often not clear which type of silica was used. Accordingly, the latest report of the European food safety authority requested additional toxicity data for well-characterised “real food-grade SAS”.To close this gap, we screened a panel of ten well-defined, food-grade SAS for potential adverse effects on differentiated Caco-2 cells. Precipitated and fumed SAS with low, intermediate and high specific surface area were included to determine structure-activity relationships.In a physiological dose-range up to 50 μg/ml and 48 h of incubation, none of the materials induced adverse effects on differentiated Caco-2 cells. This held true for endpoints of acute cytotoxicity as well as epithelial specific measures of barrier integrity. These results showed that despite considerable differences in production routes and material characteristics, food-relevant SAS did not elicit acute toxicity responses in intestinal epithelial cells. 相似文献
17.
《Regulatory toxicology and pharmacology : RTP》1999,30(2):S42-S47
The question of whether temporal equivalence can be established between test species and humans and be useful in the safety assessment of food additives has puzzled risk assessors throughout decades. The basic biological elements in any mammalian species, including humans, such as homeostasis, basal metabolism and body size/surface area, reproduction features, the timing of cellular proliferation, and aging and health as well as the relation between aging and the diet are essential in this discussion. It is concluded that exposure studies covering selected segments of the total lifetime of any animal species cannot replace lifetime studies in the same animal species in the routine safety testing of food additives, but they may in many cases turn out to become the pivotal study for the entire safety assessment. 相似文献
18.
《Critical reviews in toxicology》2013,43(5):495-537
AbstractGriseofulvin (GF) has been in use for more than 30 years as a pharmaceutical drug in humans for the treatment of dermatomycoses. Animal studies give clear evidence that it causes a variety of acute and chronic toxic effects, including liver and thyroid cancer in rodents, abnormal germ cell maturation, teratogenicity, and embroyotoxicity in various species. No sufficient data from human studies are available at present to exclude a risk in humans; therefore, attempts were made to elucidate the mechanisms responsible for the toxic effects of GF and to address the question whether such effects might occur in humans undergoing GF therapy. It is well documented that GF acts as a spindle poison and its reproductive toxicity as well as the induction of numerical chromosome aberrations and of micronuclei in somatic cells possibly may result from disturbance of microtubuli formation. Likewise, a causal relationship between aneuploidy and cancer has been repeatedly postulated. However, a critical survey of the data available on aneuploidogenic chemicals revealed insufficient evidence for such an association. Conceivably, other mechanisms may be responsible for the carcinogenic effects of the drug. The induction of thyroid tumors in rats by GF is apparently a consequence of the decrease of thyroxin levels and it is unlikely that such effects occur in GF-exposed humans. The appearance of hepatocellular carcinomas (HCC) in mice on GF-supplemented diet is preceded by various biochemical and morphological changes in the liver. Among these, hepatic porphyria is prominent, it may result from inhibition of ferrochelatase and (compensatory) induction of ALA synthetase. GF-induced accumulation of porphyrins in mouse liver is followed by cell damage and necrotic and inflammatory processes. Similar changes are known from certain human porphyrias which are also associated with an increased risk for HCC. However, the porphyrogenic effect of GF therapy in humans is moderate compared with that in the mouse model, although more detailed studies should be performed in order to clarify this relationship on a quantitative basis. A further important effect of GF-feeding in mice is the formation of Mallory bodies (MBs) in hepatocytes. These cytoskeletal abnormalities occur also in humans, although under different conditions; their appearance is associated with the induction of liver disease and HCC. Chronic liver damage associated with porphyria and MB formation, enhanced cell proliferation, liver enlargement, and enzyme induction all may contribute to the hepatocarcinogenic effect of GF in mice. In conclusion, further investigation is required for adequate assessment of health risks to humans under GF therapy. 相似文献
19.
Ylang-Ylang oil is used in the food industry as a flavor ingredient. It is a complex chemical mixture in the form of an essential oil extracted by water or water-and-steam distillation from the fresh flowers of Cananga odorata Hook. f. & Thomson. Ylang-Ylang oil has been reported to cause dermal sensitization reactions in animals and humans, but it is unclear what constituent(s) within the essential oil comprise the offending agent(s) and whether some Ylang-Ylang oils that have had certain constituent(s) removed are any less prone to cause such allergic reactions. There is no indication in the literature that food exposure to Ylang-Ylang oil has caused allergic reactions. One subchronic inhalation toxicity study, involving Ylang-Ylang oil as part of a larger fragrance raw materials mixture, gave no indication of causing adverse effects, but the relevance to risk assessment of oral food flavoring use exposures is likely minimal. No further toxicity data for Ylang-Ylang oil have been reported. Notwithstanding the foregoing, Ylang-Ylang oil has a long history of fragrance and food flavoring use, with no indication that its estimated consumption from food flavoring use (0.0001 mg/kg/day) has led to any adverse human health effects. These data indicate that at the current level of intake as a food ingredient, Ylang-Ylang oil does not pose a health risk to humans. 相似文献
20.
Acrylamide (AA) is a process-contaminant that potentially increases the risk of developing cancer in humans. AA is formed during heat treatment of starchy foods and detected in a wide range of commonly consumed products. Increased focus on risk ranking and prioritization of major causes of disease makes it relevant to estimate the impact that exposure to chemical contaminants and other hazards in food have on health. In this study, we estimated the burden of disease (BoD) caused by dietary exposure to AA, using disability adjusted life years (DALY) as health metric.We applied an exposure-based approach and proposed a model of three components: an exposure, health-outcome, and DALY-module. We estimated BoD using two approaches for estimating cancer risk based on toxicological data and two approaches for estimating DALY.In Denmark, 1.8 healthy life years per 100.000 inhabitants are lost each year due to exposure to AA through foods, as estimated by the most conservative approach.This result should be used to inform risk management decisions and for comparison with BoD of other food-borne hazards for prioritizing policies. However, our study shows that careful evaluation of methodological choices and assumptions used in BoD studies is necessary before use in policy making. 相似文献