Glyphosate herbicide formulation: a potentially lethal ingestion.

Glyphosate surfactant herbicide (GlySH) toxicity is an uncommon poisoning. We report two fatalities involving suicidal ingestion of this herbicide. Both deaths occurred despite early recognition of the serious nature of the poisoning and aggressive treatment. The deaths in this series are analysed in the context of a review of existing literature. Although traditionally regarded as minimally toxic, many deaths have been reported following suicidal ingestion. Severe GlySH toxicity may be refractory even to the most intensive supportive care. The triad of pulmonary oedema, metabolic acidosis and hyperkalaemia portends poor outcome. While containing a carbon phosphorus moiety, GlySH does not exhibit organophosphate toxicity. A clinical guide to assessing severity of GlySH toxicity is proposed and treatment modalities discussed.

Diverse taxa of cyanobacteria produce β-N-methylamino-l-alanine, a neurotoxic amino acid

Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, β-N-methylamino-l-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.

Antidiabetic drugs used in Europe prior to the discovery of insulin.

Many therapeutic agents had been used for the treatment of diabetes mellitus before insulin was discovered and several hundred plants have shown some extent of antidiabetic activity. This study tries to explore which agents were most widely used in Europe in the pre-insulin era. According to the scientific literature and the proprietary drug industry around 1900, more than 100 agents were considered to have hypoglycemic activity. Most of them seem to have been used only occasionally while some others were recommended and marketed to a large extent. Among the medicinal plants, Syzygium cumini (syn. S. jambolanum, Eugenia jambolana), Vaccinum myrtillus and Phaseolus sp. were most common, and other frequently used agents were opium, opium alkaloids, other alkaloids like quinine or Belladonna alkaloids, salicylates, alkaline substances like sodium (bi)carbonate and even strong poisons like arsenic or uranium salts. Syzygium jambolanum seed powder seems to be one of the most intensively studied antidiabetic agents of plant origin.

Hydrogen peroxide poisoning.

Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.

Aluminium and other elements in selected herbal tea plant species and their infusions.

The determination of Al, B, Cu, Fe, Mn, Ni, P, Zn and Ca, K, Mg by inductively coupled plasma optical emission spectrometry (ICP-OES) and flame atomic absorption spectroscopy (FAAS), respectively, in digests and infusions of Hibiscus sabdariffa (petals), Rosa canina (receptacles), Ginkgo biloba (leaves), Cymbopogon citratus (leaves), Aloe vera (leaves) and Panax ginseng (roots) was carried out in this study. Particular attention has been given to Al and heavy metals for the identification of possible raw material contaminants, their transformation into the infusion and for predicting their eventual role in the human diet during daily consumption. Additionally, Ion Chromatography (IC) speciation of Al in the leachates was carried out. In dry herbs, hibiscus and ginkgo appeared to contain the greatest contents of Al, Fe, K, Mn, Ni, Zn and B, Mg, P, respectively. A. vera contained the highest amount of Ca and highest values of Cu and P were observed in ginseng. In infusions, the topmost concentrations of Al, B, Cu, Fe, P, K, Mn, Ni, Zn were detected in those prepared from hibiscus petals, Ca from aloe leaves and Mg from leaves of ginkgo. According to a possible daily consumption exceeding 1 L, hibiscus decoction was identified as potentially dietetically significant in the content of certain elements. It seems to be possibly one of the top contributors of B from food (up to 5.5±0.2 mg/L). The Mg contained in the infusion (up to 106±5 mg/L) may be a contributor in the attenuation of blood pressure. A high amount of accessible Mn (up to 17.4±1.1 mg/L) can probably have an adverse effect in humans. The total Al allowance (up to 1.2±0.1 mg/L) suggests that no more than 1 L of the hibiscus infusion should be consumed per day by sensitive individuals including pregnant women and should be completely excluded from the diet of children under 6 months of age and children with chronic renal failure. Copyright © 2013 Elsevier Ltd. All rights reserved.

2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death

2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.

Ciguatera: recent advances but the risk remains.

Ciguatera is an important form of human poisoning caused by the consumption of seafood. The disease is characterised by gastrointestinal, neurological and cardiovascular disturbances. In cases of severe toxicity, paralysis, coma and death may occur. There is no immunity, and the toxins are cumulative. Symptoms may persist for months or years, or recur periodically. The epidemiology of ciguatera is complex and of central importance to the management and future use of marine resources. Ciguatera is an important medical entity in tropical and subtropical Pacific and Indian Ocean regions, and in the tropical Caribbean. As reef fish are increasingly exported to other areas, it has become a world health problem. The disease is under-reported and often misdiagnosed. Lipid-soluble, polyether toxins known as ciguatoxins accumulated in the muscles of certain subtropical and tropical marine finfish cause ciguatera. Ciguatoxins arise from biotransformation in the fish of less polar ciguatoxins (gambiertoxins) produced by Gambierdiscus toxicus, a marine dinoflagellate that lives on macroalgae, usually attached to dead coral. The toxins and their metabolites are concentrated in the food chain when carnivorous fish prey on smaller herbivorous fish. Humans are exposed at the end of the food chain. More than 400 species of fish can be vectors of ciguatoxins, but generally only a relatively small number of species are regularly incriminated in ciguatera. Ciguateric fish look, taste and smell normal, and detection of toxins in fish remains a problem. More than 20 precursor gambiertoxins and ciguatoxins have been identified in G. toxicus and in herbivorous and carnivorous fish. The toxins become more polar as they undergo oxidative metabolism and pass up the food chain. The main Pacific ciguatoxin (P-CTX-1) causes ciguatera at levels=0.1 microg/kg in the flesh of carnivorous fish. The main Caribbean ciguatoxin (C-CTX-1) is less polar and 10-fold less toxic than P-CTX-1. Ciguatoxins activate sodium ion (Na ) channels, causing cell membrane excitability and instability. Worldwide coral bleaching is now well documented, and there is a strong association between global warming and the bleaching and death of coral. This, together with natural environmental factors such as earthquakes and hurricanes, and man-made factors such as tourism, dock construction, sewage and eutrophication, may create more favourable environments for G. toxicus. While low levels of G. toxicus are found throughout tropical and subtropical waters, the presence of bloom numbers is unpredictable and patchy. Only certain genetic strains produce ciguatoxins, and environmental triggers for increasing toxin production are unknown.

Xenohormesis mechanisms underlying chemopreventive effects of some dietary phytochemicals.

A wide variety of phytochemicals present in our diet, including fruits, vegetables, and spices, have been shown to possess a broad range of health-beneficial properties. The cytoprotective and restorative effects of dietary phytochemicals are likely to result from the modulation of several distinct cellular signal transduction pathways. Many dietary phytochemicals that are synthesized as secondary metabolites function as toxins, that is, "phytoalexins," and hence protect plants against insects and other damaging organisms and stresses. However, at the relatively low doses consumed by humans and other mammals, these same toxic plant-derived chemicals, as mild stressors, activate adaptive cellular response signaling, conferring stress resistance and other health benefits. This phenomenon has been referred to as xenohormesis. This review highlights the xenohormesis mechanisms underlying chemopreventive effects of some dietary chemopreventive phytochemicals, with special focus on the nuclear transcription factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) as a key player. © 2011 New York Academy of Sciences.

Probabilistic modelling of exposure doses and implications for health risk characterization: glycoalkaloids from potatoes.

Potatoes are a source of glycoalkaloids (GAs) represented primarily by alpha-solanine and alpha-chaconine (about 95%). Content of GAs in tubers is usually 10-100 mg/kg and maximum levels do not exceed 200 mg/kg. GAs can be hazardous for human health. Poisoning involve gastrointestinal ailments and neurological symptoms. A single intake of >1-3 mg/kg b.w. is considered a critical effect dose (CED). Probabilistic modelling of acute and chronic (usual) exposure to GAs was performed in the Czech Republic, Sweden and The Netherlands. National databases on individual consumption of foods, data on concentration of GAs in tubers (439 Czech and Swedish results) and processing factors were used for modelling. Results concluded that potatoes currently available at the European market may lead to acute intakes >1 mg GAs/kg b.w./day for upper tail of the intake distribution (0.01% of population) in all three countries. 50 mg GAs/kg raw unpeeled tubers ensures that at least 99.99% of the population does not exceed the CED. Estimated chronic (usual) intake in participating countries was 0.25, 0.29 and 0.56 mg/kg b.w./day (97.5% upper confidence limit). It remains unclear if the incidence of GAs poisoning is underreported or if assumptions are the worst case for extremely sensitive persons.

Fresh aromatic herbs containing methylchavicol did not exhibit the pro-oxidative effects of pure methylchavicol on a human hepatoma cell line, HepG2.

Methylchavicol (CH(3)-CV), an important aromatic constituent of different plants like tarragon and basils, has been shown to be carcinogenic by a mechanism yet unclear, although it has been reported that carcinogenicity of CH(3)-CV in rodent might be linked to its metabolic conversion into a genotoxic electrophilic metabolite generated through a two steps bioactivation pathway catalyzed by cytochrome P450 enzymes and sulfotransferases. The induction of carcinogenesis by certain agents has been associated with the generation of oxidative stress. The aim of the present study was to determine whether pure methylchavicol applied on a human hepatoma cell line, HepG2, could promote oxidative stress and might alter the expression of procarcinogenic biomarkers such as the drug-metabolizing enzyme (CYP2E1), the inducible form of nitric oxide synthase (iNOS) and might induce the expression of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Mn-SOD that control the redox equilibrium of the cells. CH(3)-CV was shown to cause a significant induction of oxidative stress, as revealed by luminol-dependent chemiluminescence (LDCL) and to alter dramatically the expression of CYP2E1, iNOS and Mn-SOD, indicating that the toxic effect of CH(3)-CV could be mediated through a nitric oxide dependent mechanism. Under similar experimental conditions, the extracts from tarragon, chervil and basil did not induce such biological changes. These results provide evidence that the generation of an oxidative stress may be a significant event occurring during CH(3)-CV-induced toxicity. It also suggests that natural extracts containing different amounts of CH(3)-CV (tarragon, chervil and basil) did not elicit such toxicity and might contain compounds able to counteract this detrimental property. Copyright © 2012. Published by Elsevier Masson SAS.

Synergistic toxicity of the environmental neurotoxins methylmercury and β-N-methylamino-L-alanine.

Determination of the environmental factors involved in neurodegenerative diseases has been elusive. Methylmercury and β-N-methylamino-L-alanine (BMAA) have both been implicated in this role. Exposure of primary cortical cultures to these compounds independently induced concentration-dependent neurotoxicity. Importantly, concentrations of BMAA (10-100 μM) that caused no toxicity alone potentiated methylmercury (3 μM) toxicity. In addition, concentrations of BMAA and methylmercury that had no effect by themselves on the main cellular antioxidant glutathione together decreased glutathione levels. Furthermore, the combined toxicity of methylmercury and BMAA was attenuated by the cell permeant form of glutathione, glutathione monoethyl ester. The results indicate a synergistic toxic effect of the environmental neurotoxins BMAA and methylmercury, and that the interaction is at the level of glutathione depletion.

Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens

Induction of phase 2 detoxication enzymes [e.g., glutathione transferases, epoxide hydrolase, NAD(P)H: quinone reductase, and glucuronosyltransferases] is a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity of electrophiles and reactive forms of oxygen. Since consumption of large quantities of fruit and vegetables is associated with a striking reduction in the risk of developing a variety of malignancies, it is of interest that a number of edible plants contain substantial quantities of compounds that regulate mammalian enzymes of xenobiotic metabolism. Thus, edible plants belonging to the family Cruciferae and genus Brassica (e.g., broccoli and cauliflower) contain substantial quantities of isothiocyanates (mostly in the form of their glucosinolate precursors) some of which (e.g., sulforaphane or 4-methylsulfinylbutyl isothiocyanate) are very potent inducers of phase 2 enzymes. Unexpectedly, 3-day-old sprouts of cultivars of certain crucifers including broccoli and cauliflower contain 10–100 times higher levels of glucoraphanin (the glucosinolate of sulforaphane) than do the corresponding mature plants. Glucosinolates and isothiocyanates can be efficiently extracted from plants, without hydrolysis of glucosinolates by myrosinase, by homogenization in a mixture of equal volumes of dimethyl sulfoxide, dimethylformamide, and acetonitrile at −50°C. Extracts of 3-day-old broccoli sprouts (containing either glucoraphanin or sulforaphane as the principal enzyme inducer) were highly effective in reducing the incidence, multiplicity, and rate of development of mammary tumors in dimethylbenz(a)anthracene-treated rats. Notably, sprouts of many broccoli cultivars contain negligible quantities of indole glucosinolates, which predominate in the mature vegetable and may give rise to degradation products (e.g., indole-3-carbinol) that can enhance tumorigenesis. Hence, small quantities of crucifer sprouts may protect against the risk of cancer as effectively as much larger quantities of mature vegetables of the same variety.

Shared signals and the potential for phylogenetic espionage between plants and animals.

Until recently, the study and understanding of plant and animal signalling and response mechanisms have developed independently. Recent biochemical and molecular work is producing a growing list of elements involved in responses to biotic and abiotic stimuli that are very similar across kingdoms. Some of the more interesting examples of these include prostaglandin/octadecanoid-mediated responses to wounding, steroid-based signalling systems, and pathogen-recognition mechanisms. Some of these similarities probably represent evolutionary convergence; others may be ancestral to plants and animals. Ecological and evolutionary implications of such overlaps include the existence of pathogens that can cause disease in plants and animals, the ability of herbivores to manipulate plant responses, usurpation of microbial mechanisms and genes by herbivorous animals and plants, evolution of plant defenses exploiting shared signals in animals, and the medicinal use of plants by humans. Comparative study of the signalling and response mechanisms used by plants, animals, and microbes provides novel and useful insights to the ecology and evolution of interactions across kingdoms.

Ciguatera in Réunion Island (SW Indian Ocean): epidemiology and clinical patterns.

One hundred and fifty-nine ichtyosarcotoxic outbreaks, including 477 people, were recorded in the island of Réunion (SW Indian ocean) between 1986 and 1994. Ciguatera outbreaks represented 78.6% of the total cases and its annual incidence rate was estimated to be 0.78/10,000 residents. Symptoms caused by ciguatera poisoning are not different from those reported in Pacific and Caribbean islands, except for the additional symptoms of hallucinatory poisoning in 16% of the patients. Serranidae fish, including species of great commercial value, were the most commonly incriminated accounting for 50% of the outbreaks.

Studies on the antidiarrhoeal effect of dragon's blood from Croton urucurana.

The red sap obtained by slashing the bark of Croton urucurana Baill. (Euphorbiaceae), also known as dragon's blood, was screened for a possible antidiarrhoeal activity on castor oil-induced diarrhoea in rats, cholera toxin-induced intestinal secretion in mice and on small intestinal transit in mice. Dragon's blood at an oral dose of 600 mg/kg caused in marked inhibition of the diarrhoeal response following castor oil administration as well as the intestinal fluid accumulation promoted by cholera toxin. At a similar dose the red sap significantly inhibited the small intestinal transit which was, however, found to be independent of the opioid mechanism. These results suggest a potential usefulness of the red sap from Croton urucurana Baill. in the control of secretory diarrhoea associated pathologies. Copyright 2001 John Wiley & Sons, Ltd.

A human dietary risk assessment associated with glycoalkaloid responses of potato to Colorado potato beetle defoliation.

A quantitative human dietary risk assessment was conducted using the glycoalkaloid concentrations measured from tubers of plants defoliated by Colorado potato beetles and undefoliated (control). There was a significantly greater production of glycoalkaloids for defoliated plants compared to control plants for both skin and inner tissue of tubers. The dietary risk posed to different human subgroups associated with the consumption of potatoes was estimated for the 50th, 95th, and 99.9th percentile US national consumption values. Exposures were compared to a toxic threshold of 1.0mg/kg body weight. Defoliation by Colorado potato beetles increased dietary risk by approximately 48%. Glycoalkaloid concentrations within the inner tissue of tubers, including undefoliated controls, exceeded the toxic threshold for all human subgroups at less than the 99.9th percentile of exposure, but not the 95th percentile.

Detection of toxic heavy metals and pesticide residue in herbal plants which are commonly used in the herbal formulations.

Herbal formulations are getting popular throughout the world and commercialized extensively for various medicinal properties. WHO has emphasized the need for quality assurance of herbal products, including testing of heavy metals and pesticides residues. In view of WHO guidelines, single herbal drugs used in herbal formulations were collected from local market, for testing heavy metals and persistent pesticides residue. Therefore, in the present case, we have examined few local samples of certain herbs viz. Emblica officinalis, Terminalia chebula, Terminalia belerica, and Withania somnifera. The present studies were selected for estimation of four heavy metals namely Arsenic, Cadmium, Lead, and Mercury. Apart from these, pesticide residue Viz. Organochlorine pesticides, Organophosphorus pesticides, and Pyrethroids were analyzed in the four samples of single crude drugs. Heavy metals and pesticide residue were found below detection limits in all the samples.

Exposure to beta-carbolines norharman and harman.

The aromatic beta-carbolines norharman and harman have been implicated in a number of human diseases including Parkinson's disease, tremor, addiction and cancer. It has been shown that these compounds are normal body constituents formed endogenously but external sources have been identified. Here, we summarise literature data on levels of norharman and harman in fried meat and fish, meat extracts, alcoholic drinks, and coffee brews. Other sources include edible and medicinal plants but tobacco smoke has been identified as a major source. Exposure levels from these different dietary sources are estimated to a maximum of 4 microg norharman per kg body weight (bw) per day and 1 microg harman per kg bw per day. Exposure via tobacco smoke depends on smoking habits and type of cigarettes but can be estimated to 1.1 microg/kg bw for norharman and 0.6 microg/kg bw for harman per package of cigarettes smoked. Studies on toxicokinetics indicate that inhalative exposure leads to a rapid increase in plasma levels and high bioavailability of norharman and harman. Oral bioavailability is lower but there are indications that sublingual absorption may increase dietary uptake of beta-carbolines. Endogenous formation can be estimated to be 50-100 ng/kg bw per day for norharman and about 20 ng/kg bw per day for harman but these rates may increase with high intake of precursors. Biomarker studies on plasma levels of beta-carbolines reported on elevated levels of norharman, harman or both in diseased patients, alcoholics and following tobacco smoking or consumption of beta-carboline-containing food. Cigarette smoking has been identified as major influence but dietary exposure may contribute to exposure.

Radioprotection by plant products: present status and future prospects.

The development of radioprotective agents has been the subject of intense research in view of their potential for use within a radiation environment, such as space exploration, radiotherapy and even nuclear war. However, no ideal, safe synthetic radioprotectors are available to date, so the search for alternative sources, including plants, has been on going for several decades. In Ayurveda, the traditional Indian system of medicine, several plants have been used to treat free radical-mediated ailments and, therefore, it is logical to expect that such plants may also render some protection against radiation damage. A systematic screening approach can provide leads to identifying potential new candidate drugs from plant sources, for mitigation of radiation injury. This article reviews some of the most promising plants, and their bioactive principles, that are widely used in traditional systems of medicine, and which have rendered significant radioprotection in both in vitro and in vivo model systems. Plants and their constituents with pharmacological activities that may be relevant to amelioration of radiation-mediated damage, including antiemetic, antiinflammatory, antioxidant, cell proliferative, wound healing and haemopoietic stimulatories are also discussed. Copyright (c) 2005 John Wiley & Sons, Ltd.

The toxicity of extracts of plant parts of Moringa stenopetala in HEPG2 cells in vitro.

The cytotoxicity of extracts from a widely used species of plant, Moringa stenopetala, was assessed in HEPG2 cells, by measuring the leakage of lactate dehydrogenase (LDH) and cell viability. The functional integrity of extract-exposed cells was determined by measuring intracellular levels of ATP and glutathione (GSH). The ethanol extracts of leaves and seeds increased significantly (p < 0.01) LDH leakage in a dose- and time-dependent manner. The water extract of leaves and the ethanol extract of the root did not increase LDH leakage. A highly significant (p < 0.001) decrease in HEPG2 viability was found after incubating the cells with the highest concentration (500 microg/mL) of the ethanol leaf and seed extracts. At a concentration of 500 microg/mL, the water extract of leaves increased (p < 0.01), while the ethanol extract of the same plant part decreased (p < 0.01), ATP levels. The root and seed extracts had no significant effect on ATP levels. The ethanol leaf extract decreased GSH levels at a concentration of 500 microg/mL (p < 0.01), as did the ethanol extract of the seeds at 250 microg/mL and 500 microg/mL (p < 0.05). The water extract of the leaves did not alter GSH or LDH levels or affect cell viability, suggesting that it may be non-toxic, and is consistent with its use as a vegetable. The data obtained from the studies with the ethanol extract of the leaves and seeds from Moringa stenopetala show that they contain toxic substances that are extractable with organic solvents or are formed during the process of extraction with these solvents. The significant depletion of ATP and GSH only occurred at concentrations of extract that caused leakage of LDH. Further investigation with this plant in order to identify the constituents extracted and their individual toxic effects both in vivo and in vitro is warranted. This study also illustrates the utility of cell culture for screening plant extracts for potential toxicity. Copyright (c) 2005 John Wiley & Sons, Ltd.

Aluminium in over-the-counter drugs: risks outweigh benefits?

In the early 1970s, aluminium toxicity was first implicated in the pathogenesis of clinical disorders in patients with chronic renal failure involving bone (renal osteomalacia) or brain tissue (dialysis encephalopathy). Before that time the toxic effects of aluminium ingestion were not considered to be a major concern because absorption seemed unlikely to occur. Meanwhile, aluminium toxicity has been investigated in countless epidemiological and clinical studies as well as in animal experiments and many papers have been published on the subject. It is now commonly acknowledged that aluminium toxicity can be induced by infusion of aluminium-contaminated dialysis fluids, by parenteral nutrition solutions, and by oral exposure as a result of aluminium-containing pharmaceutical products such as aluminium-based phosphate binders or antacid intake. Over-the-counter antacids are the most important source for human aluminium exposure from a quantitative point of view. However, aluminium can act as a powerful neurological toxicant and provoke embryonic and fetal toxic effects in animals and humans after gestational exposure. Despite these facts, the patient information leaflets from European antacids that are available OTC show substantial differences regarding warnings from aluminium toxicity. It seems advisable that all patients should receive the same information on aluminium toxicity from patient information leaflets, in particular with regard to the increased absorption through concomitant administration with citrate-containing beverages and the use of such antacids during pregnancy.

The many faces of methylmercury poisoning.

Methylmercury (MM) is a very potent neurotoxic agent. Its role in polluting the environment is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. Exposure to MM may be through ingestion of poisoned fish or inadvertent misuse of grain treated with the poison as a fungicide. Major epidemics have occurred in Japan (Fetal Minamata disease), Iraq, Pakistan, Guatemala, and Ghana. Sporadic incidences have occurred in the United States and Canada. There is no effective antidote to counteract the effect of MM on the central nervous system, although the information documented should provide hope for more effective therapy in acute cases.

Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats.

The acute and subacute toxicity of five biogenic amines-tyramine, spermidine, spermine, putrescine and cadaverine-were examined in Wistar rats. Tyramine and cadaverine had a low acute oral toxicity of more than 2000 mg/kg body weight. Putrescine had an acute oral toxicity of 2000 mg/kg body weight and spermidine and spermine each of 600 mg/kg body weight. All amines investigated caused a dose-related decrease in blood pressure after intravenous administration, except for tyramine, where an increase was found. In 6-wk studies the biogenic amines were administered in the diet to groups of 10 male and 10 female rats. Tyramine and cadaverine were given at levels of 0, 200, 2000 or 10,000 ppm, spermine and putrescine at levels of 0, 200, 2000 or 5000 ppm and spermidine at levels of 0, 20, 200 or 500/1000 ppm in the first study and at levels of 0 or 10,000 ppm in a second study. Spermine was the most toxic. The high dose level showed a great number of changes, such as emaciation, aggressiveness, convulsions and paralysis of the hind legs. Growth, food intake and water intake were considerably decreased. Slight anaemia (males) and changes in plasma clinical chemistry occurred. The relative weights of the thyroid, adrenals, spleen and heart were increased and that of the liver decreased. Impaired kidney function, together with renal histopathological changes and changes in plasma electrolytes and urea, occurred with spermine. Histopathological examinations also revealed decreased glycogen content in the liver, reduction of spermatogenesis, severe depletion of splenic white pulp, acute involution of the thymus and moderate myocardial degeneration in the heart. Myocardial degeneration was also seen in one mid-dose male. Adverse effects were also observed in the top dose groups of all other amines. Decreased body weights associated with diminished food intake were generally seen. Slight increases in packed cell volume, haemoglobin concentration and thrombocytes occurred with cadaverine. With spermidine, decreased plasma creatinine, calcium and inorganic phosphate were observed and decreased potassium levels with cadaverine. The no-observed-adverse-effect level was 2000 ppm (180 mg/kg body weight/day) for tyramine, cadaverine and putrescine, 1000 ppm (83 mg/kg body weight/day) for spermidine and 200 ppm (19 mg/kg body weight/day) for spermine.

Artemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety.

Artemisia dracunculus L. (tarragon) has a long history of use as a spice and remedy. Two well-described "cultivars" (Russian and French) are used widely and differ in ploidy level, morphology, and chemistry. Key biologically active secondary metabolites are essential oils (0.15-3.1%), coumarins (>1%), flavonoids, and phenolcarbonic acids. In vivo studies mainly in rodents, particularly from Russian sources, highlight potential anti-inflammatory, hepatoprotective, and antihyperglycemic effects. Despite concerns about the toxic effects of two of its main constituents, estragole (up to 82%) and methyleugenol (up to 39%), no acute toxicity or mutagenic activity has been reported at doses relevant for human consumption. Water extracts of A. dracunculus contain very low amounts of estragole and methyleugenol and, therefore, are considered to pose a very limited risk. Overall, a stronger focus on clinical studies and precise taxonomic and phytochemical definition of the source material will be essential for future research efforts.

Male reproductive organs are at risk from environmental hazards

Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer. Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However, the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation, radiant heat and a number of known toxicants. So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world. For other toxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones. Finally, there are data indicating a particular vulnerability of the fetal testis to toxicants—for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.

Acute and Sub-Acute Toxicological Assessment of the Aqueous Seed Extract of Persea Americana Mill (Lauraceae) in Rats

The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD50) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD50 could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

A literature review on the safety assessment of genetically modified plants.

In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.

Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer.

Emblica officinalis Gaertn. or Phyllanthus emblica Linn, commonly known as Indian gooseberry or amla, is arguably the most important medicinal plant in the Indian traditional system of medicine, the Ayurveda. Various parts of the plant are used to treat a range of diseases, but the most important is the fruit. The fruit is used either alone or in combination with other plants to treat many ailments such as common cold and fever; as a diuretic, laxative, liver tonic, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory, hair tonic; to prevent peptic ulcer and dyspepsia, and as a digestive. Preclinical studies have shown that amla possesses antipyretic, analgesic, antitussive, antiatherogenic, adaptogenic, cardioprotective, gastroprotective, antianemia, antihypercholesterolemia, wound healing, antidiarrheal, antiatherosclerotic, hepatoprotective, nephroprotective, and neuroprotective properties. In addition, experimental studies have shown that amla and some of its phytochemicals such as gallic acid, ellagic acid, pyrogallol, some norsesquiterpenoids, corilagin, geraniin, elaeocarpusin, and prodelphinidins B1 and B2 also possess antineoplastic effects. Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities, properties that are efficacious in the treatment and prevention of cancer. This review for the first time summarizes the results related to these properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a cancer preventive and therapeutic drug in humans.

Death by polonium-210: lessons learned from the murder of former Soviet spy Alexander Litvinenko.

The medical response to radiation--whether the result of radiological warfare, terrorist deployment of improvised radiation dispersal weapons, political assassination, occupational or industrial accidents or the medically radiated patient remains one of the least taught among all disciplines within medical education. In the aftermath of 9/11 among medical vulnerabilities to toxicant threats, of all the categories of weapons of mass destruction (WMD)--whether using the CBRNE (chemical, biological, radiological, nuclear, explosive) or NBC (nuclear, biological, chemical) acronym--radiation is the least taught in professional schools, responder cultures or civil preparedness organizations. To date, few health care professionals (HCP) possess the fundamental knowledge or skills to identify and diagnose, let alone treat a radiation victim; this vulnerability made even more obvious in the aftermath of the high profile assassination of former Russian agent Alexander Litvinenko. He was poisoned with Polonium210. Radioactive substances are ubiquitous with radiation sources being in or transported through virtually every region nationwide. It is essential to increase preparedness among community and rural health care facilities as well as urban and university hospitals. Managing radiation injuries effectively requires access to specialized equipment and expertise. Radiation sickness is progressive and may require acute, critical and long-term care throughout the course of illness. Regardless of the source, preparedness rests upon acknowledging a threat exists and dedicating the resources to address the risks including the enhancement of training and equipment. Mass or individual exposures to radiation present unique challenges to the entire response continuum from law enforcement, first responders and emergency medical care. Increased education about and practice in responding to radiological threats is essential to enhance preparedness.

Potato glycoalkaloids: true safety or false sense of security?

As one of the major agricultural crops, the cultivated potato is consumed each day by millions of people from diverse cultural backgrounds. A product of global importance, the potato tuber contains toxic glycoalkaloids (GAs) that cause sporadic outbreaks of poisoning in humans, as well as many livestock deaths. This article will discuss some aspects of the potato GAs, including their toxic effects and risk factors, methods of detection of GAs and biotechnological aspects of potato breeding. An attempt has been made to answer a question of vital importance - are potato GAs dangerous to humans and animals and, if so, to what extent?

Heavy metals in wild rice from northern Wisconsin.

Wild rice grain samples from various parts of the world have been found to have elevated concentrations of heavy metals, raising concern for potential effects on human health. It was hypothesized that wild rice from north-central Wisconsin could potentially have elevated concentrations of some heavy metals because of possible exposure to these elements from the atmosphere or from water and sediments. In addition, no studies of heavy metals in wild rice from Wisconsin had been performed, and a baseline study was needed for future comparisons. Wild rice plants were collected from four areas in Bayfield, Forest, Langlade, Oneida, Sawyer and Wood Counties in September, 1997 and 1998 and divided into four plant parts for elemental analyses: roots, stems, leaves and seeds. A total of 194 samples from 51 plants were analyzed across the localities, with an average of 49 samples per part depending on the element. Samples were cleaned of soil, wet digested, and analyzed by ICP for Ag, As, Cd, Cr, Cu, Hg, Mg, Pb, Se and Zn. Roots contained the highest concentrations of Ag, As, Cd, Cr, Hg, Pb, and Se. Copper was highest in both roots and seeds, while Zn was highest just in seeds. Magnesium was highest in leaves. Seed baseline ranges for the 10 elements were established using the 95% confidence intervals of the medians. Wild rice plants from northern Wisconsin had normal levels of the nutritional elements Cu, Mg and Zn in the seeds. Silver, Cd, Hg, Cr, and Se were very low in concentration or within normal limits for food plants. Arsenic and Pb, however, were elevated and could pose a problem for human health. The pathway for As, Hg and Pb to the plants could be atmospheric.

Toxicology of nutmeg abuse.

BACKGROUND: Unpleasant and frightening side effects associated with the abuse of nutmeg occasionally generate emergency department referrals. We report a young patient's first-time experience with nutmeg and review the mechanisms of its toxicity. CASE REPORT: A 13-year-old female ingested 15-24 g of nutmeg over a 3-hour period and smoked and shared 2 joints of marijuana. To facilitate ingestion, the nutmeg was put into 00-000 gelatin capsules. Bizarre behavior and visual, auditory, and tactile hallucinations developed. She also experienced nausea, gagging, hot/cold sensations, and blurred vision followed by numbness, double, and "triple" vision, headache, and drowsiness. Nystagmus, muscle weakness, and ataxia were present. Her vital signs and laboratory tests were normal. She received 50 g of activated charcoal and except for complaints of dizziness and visual changes, her 2-day admission was uneventful. The central nervous system activity of nutmeg is often postulated to result from biotransformation of its chemical components to amphetamine-like compounds, but this has not been proven. Nutmeg contains several compounds with structural similarities to substances with known central nervous system neuromodulatory activity.

Monitoring of mercury, arsenic, and lead in traditional Asian herbal preparations on the Dutch market and estimation of associated risks.

Traditional herbal preparations used in Ayurveda, traditional Chinese medicine, traditional Tibetan medicine, and other Asian traditional medicine systems may contain significant amounts of mercury, arsenic or lead. Though deliberately incorporated in Asian traditional herbal preparations for therapeutic purposes, these constituents have caused intoxications worldwide. The aim of this study was therefore to determine mercury, arsenic, and lead levels in Asian traditional herbal preparations on the Dutch market. A total of 292 traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine were sampled between 2004 and 2007. Samples were mostly multi-ingredient traditional herbal preparations containing herbs and minerals. The labeling of less than 20% of the traditional herbal preparations suggested the presence of mercury, arsenic or lead. These elements were shown by inductively coupled mass spectrometry (ICP-MS) in 186 (64%) of 292 traditional herbal preparations. Estimated weekly mercury, arsenic, and lead intake levels were calculated for each traditional herbal preparation from the analytically determined concentrations and the recommended dose. A total of 59 traditional herbal preparations (20%) were likely to result in intakes of these elements significantly exceeding safety limits. Of these 59 traditional herbal preparations, intake estimates for 50 traditional herbal preparations significantly exceeded the safety limit for mercury (range = 1.4-1747 mg week(-1)); intake estimates for 26 traditional herbal preparations significantly exceeded the safety limit for arsenic (range = 0.53-427 mg week(-1)) and intake estimates for eight traditional herbal preparations were significantly above the safety limit for lead (range = 2.6-192 mg week(-1)). It is concluded that the mercury, arsenic, and lead contents of traditional herbal preparations used in Ayurveda, traditional Chinese medicine, and traditional Tibetan medicine remain a cause for concern and require strict control.

Time- and dose-dependent effects of roundup on human embryonic and placental cells.

Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.

Immunity: plants as effective mediators.

In the domain of nutrition, exploring the diet-health linkages is major area of research. The outcomes of such interventions led to widespread acceptance of functional and nutraceutical foods; however, augmenting immunity is a major concern of dietary regimens. Indeed, the immune system is incredible arrangement of specific organs and cells that enabled humans to carry out defense against undesired responses. Its proper functionality is essential to maintain the body homeostasis. Array of plants and their components hold immunomodulating properties. Their possible inclusion in diets could explore new therapeutic avenues to enhanced immunity against diseases. The review intended to highlight the importance of garlic (Allium sativum), green tea (Camellia sinensis), ginger (Zingiber officinale), purple coneflower (Echinacea), black cumin (Nigella sativa), licorice (Glycyrrhiza glabra), Astragalus and St. John's wort (Hypericum perforatum) as natural immune boosters. These plants are bestowed with functional ingredients that may provide protection against various menaces. Modes of their actions include boosting and functioning of immune system, activation and suppression of immune specialized cells, interfering in several pathways that eventually led to improvement in immune responses and defense system. In addition, some of these plants carry free radical scavenging and anti-inflammatory activities that are helpful against cancer insurgence. Nevertheless, interaction between drugs and herbs/botanicals should be well investigated before recommended for their safe use, and such information must be disseminated to the allied stakeholders.

Coriander (Coriandrum sativum L.): a potential source of high-value components for functional foods and nutraceuticals--a review.

Coriander (Coriandrum sativum L.), a herbal plant, belonging to the family Apiceae, is valued for its culinary and medicinal uses. All parts of this herb are in use as flavoring agent and/or as traditional remedies for the treatment of different disorders in the folk medicine systems of different civilizations. The plant is a potential source of lipids (rich in petroselinic acid) and an essential oil (high in linalool) isolated from the seeds and the aerial parts. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb, which include anti-microbial, anti-oxidant, anti-diabetic, anxiolytic, anti-epileptic, anti-depressant, anti-mutagenic, anti-inflammatory, anti-dyslipidemic, anti-hypertensive, neuro-protective and diuretic. Interestingly, coriander also possessed lead-detoxifying potential. This review focuses on the medicinal uses, detailed phytochemistry, and the biological activities of this valuable herb to explore its potential uses as a functional food for the nutraceutical industry. Copyright © 2012 John Wiley & Sons, Ltd.

Domoic acid and human exposure risks: a review.

Domoic acid is a potent neurotoxin that is naturally produced by several diatom species of the genus Pseudo-nitzschia. The toxin acts as a glutamate agonist and is excitotoxic in the vertebrate central nervous system and other glutamate receptor-rich organs. Human exposure to domoic acid occurs via the consumption of contaminated shellfish that have accumulated the toxin while filter feeding on toxigenic phytoplankton during blooms. The first reported human domoic acid poisoning event occurred in Canada in 1987 during which clinical signs of acute toxicity such as gastrointestinal distress, confusion, disorientation, memory loss, coma and death were observed. The illness was named amnesic shellfish poisoning (ASP) and due to effective seafood monitoring programs there have been no documented ASP cases since 1987. However, domoic acid poisoning has a significant effect on marine wildlife and multiple poisoning events have occurred in marine birds and mammals over the last few decades. Currently, domoic acid producing diatom blooms are thought to be increasing in frequency world wide, posing an increasing threat to wildlife and human health. Of particular concern are the potential impacts of long-term low-level exposure in "at risk" human populations. The impacts of repetitive low-level domoic acid exposure are currently unknown. This review provides a basic description of the mechanism of action of domoic acid as well as a synthesis of information pertaining to domoic acid exposure routes, toxin susceptibility, and the importance of effective monitoring programs. The importance of investigating the potential human health impacts of long-term low-level domoic acid exposure in "at risk" human populations is also discussed. Published by Elsevier Ltd.

A systematic screening of total antioxidants in dietary plants.

A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.

Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam.

The Chamorro people of Guam have been afflicted with a complex of neurodegenerative diseases (now known as ALS-PDC) with similarities to ALS, AD, and PD at a far higher rate than other populations throughout the world. Chamorro consumption of flying foxes may have generated sufficiently high cumulative doses of plant neurotoxins to result in ALS-PDC neuropathologies, since the flying foxes forage on neurotoxic cycad seeds.

Amnesic shellfish poison.

Amnesic shellfish poisoning (ASP) is caused by consumption of shellfish that have accumulated domoic acid, a neurotoxin produced by some strains of phytoplankton. The neurotoxic properties of domoic acid result in neuronal degeneration and necrosis in specific regions of the hippocampus. A serious outbreak of ASP occurred in Canada in 1987 and involved 150 reported cases, 19 hospitalisations and 4 deaths after consumption of contaminated mussels. Symptoms ranged from gastrointestinal disturbances, to neurotoxic effects such as hallucinations, memory loss and coma. Monitoring programmes are in place in numerous countries worldwide and closures of shellfish harvesting areas occur when domoic acid concentrations exceed regulatory limits. This paper reviews the chemistry, sources, metabolism and toxicology of domoic acid as well as human case reports of ASP and discusses a possible mechanism of toxicity.

Bach flower remedies: a systematic review of randomised clinical trials.

Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos.

Toxicology and risk assessment of coumarin: focus on human data.

Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.

Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells.

Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Anthocyanins exist widely in many vegetables and fruits. Some reports demonstrated that anthocyanins extracted from H. sabdariffa L., Hibiscus anthocyanins (HAs) (which are a group of natural pigments existing in the dried calyx of H. sabdariffa L.) exhibited antioxidant activity and liver protection. Therefore, in this study, we explored the effect of HAs on human cancer cells. The result showed that HAs could cause cancer cell apoptosis, especially in HL-60 cells. Using flow cytometry, we found that HAs treatment (0-4 mg/ml) markedly induced apoptosis in HL-60 cells in a dose- and time-dependent manner. The result also revealed increased phosphorylation in p38 and c-Jun, cytochrome c release, and expression of tBid, Fas, and FasL in the HAs-treated HL-60 cells. We further used SB203580 (p38 inhibitor), PD98059 (MEK inhibitor), SP600125 (JNK inhibitor), and wortmannin (phosphatidylinositol 3-kinase; PI-3K inhibitor) to evaluate their effect on the HAs-induced HL-60 death. The data showed that only SB203580 had strong potential in inhibiting HL-60 cell apoptosis and related protein expression and phosphorylation. Therefore, we suggested that HAs mediated HL-60 apoptosis via the p38-FasL and Bid pathway. According to these results, HAs could be developed as chemopreventive agents. However, further investigations into the specificity and mechanism(s) of HAs are needed.

Ginger in the prevention of nausea and vomiting: a review.

Nausea and vomiting are physiological processes experienced by every human being at some stage of their life. They are complex protective mechanisms and the symptoms are influenced by the emetogenic response and stimuli. However, when these symptoms recur frequently, they can significantly reduce the quality of life and can also be detrimental to health. The existing antiemetic agents are ineffective against certain stimuli, are expensive, and possess side effects. Herbal medicines have been shown to be effective antiemetics, and among the various plants studied, the rhizome of Zingiber officinale, commonly known as ginger, has been used as a broad-spectrum antiemetic in the various traditional systems of medicine for over 2000 years. Various preclinical and clinical studies have shown ginger to possess antiemetic effects against different emetogenic stimuli. However, conflicting reports especially in the prevention of chemotherapy-induced nausea and vomiting and motion sickness prevent us from drawing any firm conclusion. The current review for the first time summarizes the results. An attempt is also made to address the lacunae in these published studies and emphasize aspects that need further investigations for it to be of use in clinics in the future.

Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin.

Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the physiological levels in human.

Herbal infusions as a source of calcium, magnesium, iron, zinc and copper in human nutrition.

The study material consisted of five herbs: chamomile (flowers), mint (leaves), St John's wort (flowers and leaves), sage (leaves) and nettle (leaves), sourced from three producers. The calcium, magnesium, iron, zinc and copper contents were determined for both dried herb samples and prepared infusions, and the extraction rates were calculated. Mineral components were determined using atomic absorption spectrometry. Analysis showed that the contents of individual elements in herbs and infusions depended on the type of raw material, as well as on its origin. Moreover, it was found that iron penetrated the herbal infusions to the lowest degree (4.4-12.4%), while copper did so to the highest (26.7-50.7%). It is felt that in average consumption the herbal infusions are not important as calcium, magnesium, iron, zinc and copper sources in human nutrition.

Phytochemicals and cancer risk: a review of the epidemiological evidence.

A number of epidemiological studies have investigated associations between various phytochemicals and cancer risk. Phytoestrogens and carotenoids are the two most commonly studied classes of phytochemicals; phytosterols, isothiocyanates, and chlorophyll also have been investigated, although to a much lesser extent. Because there have been no systematic reviews of the literature on all phytochemicals and cancer risk to date, this article systematically reviews 96 published epidemiological studies that examined associations between phytochemicals and cancer risk. Most studies found null associations between individual phytochemicals and cancer risk at various sites. In addition, results from past studies have been largely inconsistent, and observed associations have been of relatively modest magnitude. The most consistent protective effects were observed for higher levels--dietary intake, serum, plasma, or urinary metabolites--of β-carotene and renal cell cancer, β-cryptoxanthin and lung cancer, isothiocyanates and lung cancer, isothiocyanates and gastrointestinal cancer, lignans and postmenopausal breast cancer, and flavonoids and lung cancer. Although elevated risk of certain cancers with higher levels of certain phytochemicals was observed, an insufficient pool of studies examining the same associations or inconsistent findings across studies limit the ability to conclude that any one phytochemical increases cancer risk. Additional research is needed to support previously identified associations in cases where only one study has examined a particular relationship. Importantly, continued research efforts are needed to evaluate the cumulative and interactive effects of numerous phytochemicals and phytochemical-rich foods on cancer risk.

Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells.

Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanism of action of stinging nettles.

OBJECTIVE: Inadvertent exposure to the ubiquitous weed, Urtica dioica, called "stinging nettles" produces an immediate stinging and burning sensation on the skin. This investigation evaluates the structural effect that stinging nettle spicules may have on the clinical manifestation of these symptoms. This hypothesis was investigated by exposing murine skin to stinging nettles and then evaluating the skin using electron microscopy. It was hypothesized that the mechanism of action of stinging nettles is both biochemical and mechanical, which may have clinical significance regarding treatment for acute exposure. METHODS: Fresh post-mortem dermis samples from the carcasses of genetically modified hairless mice were brushed under the stem and leaf of a stinging nettle plant, mimicking the clinical method of exposure a patient might experience. Another set of mouse skin samples was obtained but not exposed to the nettles. Both sets of skin samples were imaged with scanning electron microscopy. RESULTS: The skin samples that were not exposed to nettle leaves were uniform, with occasional striated hairs on the skin surface and no nettle spicules. The skin samples exposed to nettle leaves showed many smooth nettle spicules piercing the skin surface. A few spicules retained their bases, which appear empty of any liquid contents. CONCLUSIONS: The mechanism of action of stinging nettles dermatitis appears to be both biochemical and mechanical. Impalement of spicules into the skin likely accounts for the mechanical irritation in addition to the known adverse chemical effects of stinging nettles. Further investigation of treatment modalities is warranted. Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Potential risks resulting from fruit/vegetable-drug interactions: effects on drug-metabolizing enzymes and drug transporters.

It has been well established that complex mixtures of phytochemicals in fruits and vegetables can be beneficial for human health. Moreover, it is becoming increasingly apparent that phytochemicals can influence the pharmacological activity of drugs by modifying their absorption characteristics through interactions with drug transporters as well as drug-metabolizing enzyme systems. Such effects are more likely to occur in the intestine and liver, where high concentrations of phytochemicals may occur. Alterations in cytochrome P450 and other enzyme activities may influence the fate of drugs subject to extensive first-pass metabolism. Although numerous studies of nutrient-drug interactions have been published and systematic reviews and meta-analyses of these studies are available, no generalizations on the effect of nutrient-drug interactions on drug bioavailability are currently available. Several publications have highlighted the unintended consequences of the combined use of nutrients and drugs. Many phytochemicals have been shown to have pharmacokinetic interactions with drugs. The present review is limited to commonly consumed fruits and vegetables with significant beneficial effects as nutrients and components in folk medicine. Here, we discuss the phytochemistry and pharmacokinetic interactions of the following fruit and vegetables: grapefruit, orange, tangerine, grapes, cranberry, pomegranate, mango, guava, black raspberry, black mulberry, apple, broccoli, cauliflower, watercress, spinach, tomato, carrot, and avocado. We conclude that our knowledge of the potential risk of nutrient-drug interactions is still limited. Therefore, efforts to elucidate potential risks resulting from food-drug interactions should be intensified in order to prevent undesired and harmful clinical consequences. © 2011 Institute of Food Technologists®

Effects of sorbic acid and its salts on chromosome aberrations, sister chromatid exchanges and gene mutations in cultured Chinese hamster cells.

The ability of sorbic acid and its potassium and sodium salts to induce chromosome aberrations, sister chromatid exchanges (SCE) and gene mutations in cultured Chinese hamster V79 cells was examined. Sodium sorbate caused significant induction of chromosome aberrations and SCE, and also induced 6-thioguanine-resistant mutations in a dose-dependent manner. The clastogenic potency of sodium sorbate was found to be less than one hundredth of that of the potent clastogen N-methyl-N'-nitro-N-nitrosoguanidine. The induction of SCE by sodium sorbate was twice the control level, whereas that by methyl methanesulphonate, a potent inducer of SCE, was 14 times the control level. The mutagenic potency of sodium sorbate was less than one-tenth that of ethyl methanesulphonate, a potent inducer of mutation, when compared at an equitoxic level. Sorbic acid and its potassium salt induced chromosome aberrations, but only at the highest doses tested. These compounds also induced 1.2 times the control level of SCE, but neither compound induced 6-thioguanine-resistant mutations. The cytogenetic activity of sodium sorbate was concluded not to be due to the effect of osmotic pressure or an impurity. These results indicate that sodium sorbate is a genotoxic agent, although its potency seems to be weak, and that sorbic acid and potassium sorbate are less genotoxic than the sodium salt.

Methylmercury: A Potential Environmental Risk Factor Contributing to Epileptogenesis

Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility.

First detection of anatoxin-a in human and animal dietary supplements containing cyanobacteria.

Anatoxin-a is a potent neurotoxin produced by several species of cyanobacteria. This alkaloid may cause fatal intoxication to exposed organisms and this has raised concerns over the increasing popularity of food supplements containing cyanobacteria. These are being marketed with alleged health properties for animal and human consumption. These supplements most commonly contain the genera Spirulina (Arthrospira) and Aphanizomenon and their consumption represent a potential route for anatoxin-a exposure in cases where adequate quality control is not undertaken. In this work, several dietary supplements containing cyanobacteria from different commercial suppliers were evaluated for the presence of anatoxin-a by high performance liquid chromatography with fluorescence detection. Additionally, the presence of the previously derivatized anatoxin-a was confirmed by using Gas chromatography-mass spectrometry. A total of 39 samples were analysed in the study. Results showed that three of the samples (7.7%) contained anatoxin-a, at concentrations ranging from 2.50 to 33 microg g(-1). Quality control of cyanobacterial food supplements is required to avoid potential health effects in humans and animals.

Accidental bullous phototoxic reactions to bergamot aromatherapy oil.

Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP]). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.

Application of LC and LC-MS to the analysis of melatonin and serotonin in edible plants.

Melatonin is a neurohormone produced by the pineal gland of animals. Serotonin is a monoamine neurotransmitter and one of the precursors of melatonin biosynthesis. These two indoleamines have recently been reported to have widespread occurrence in many edible plants. Consuming foodstuffs containing melatonin and serotonin could raise their physiologic concentrations in blood and enhance human health. Literature concerning analytical methods suitable for determination of melatonin and serotonin in edible plants is limited, although several liquid chromatographic (LC) techniques have been used for their quantification. Liquid chromatography-mass spectrometry (LC-MS) methods combine selectivity, sensitivity, and high precision, and enable the simultaneous determination of melatonin and serotonin. This work reviews LC and LC-MS techniques used to determine melatonin and serotonin, and the available data on melatonin and serotonin levels in edible plants. © 2011 Crown Copyright

A case of fatal caffeine poisoning.

Caffeine is a natural alkaloid methylxanthine that is found in various plants such as coffee or tea. Symptoms of a severe overdose may present with hypokalemia, hyponatremia, ventricular arrhythmias, hypertension followed by hypotension, respiratory failure, seizures, rhabdomyolysis, ventricular fibrillation and finally circulatory collapse. A 21-year-old woman called for the ambulance herself soon after the ingestion of about 10,000 mg of caffeine. At the arrival of the ambulance, the patient went into cardiac arrest almost immediately. After a total resuscitation period of 34 min including seven counter-shocks and 2 mg epinephrine, the patient was stable enough to be transferred to the hospital. The patient soon went into VF again and received two more counter-shocks and 1 mg epinephrine and finally an intravenous bolus dose of 300 mg amiodarone. The initial arterial blood gas showed pH at 6.47, lactate at 33 mmol/l and potassium level at 2.3 mmol/l. Unfortunately, no blood samples for caffeine analysis were taken. Three days after hospital admission, the patient developed myoclonus, which did not respond to medical treatment. Excessive intake of caffeine may produce arrhythmias and pronounced hypokalemia and ensuing ventricular fibrillation. In case of counter-shock-resistant VF, it can be necessary to give an early loading dose of amiodarone. Furthermore, it may be beneficial to replace the potassium as early as possible. Epinephrine and buffer solutions used during resuscitation may further decrease blood potassium levels and should be administrated cautiously. Epinephrine can be replaced by other vasopressor drugs, such as vasopressin without effects on beta-receptors.

Heavy metals in commercial fish in New Jersey.

Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. While attention has focused on self-caught fish, most of the fish eaten by the American public comes from commercial sources. We sampled 11 types of fish and shellfish obtained from supermarkets and specialty fish markets in New Jersey and analyzed them for arsenic, cadmium, chromium, lead, manganese, mercury, and selenium. We test the null hypothesis that metal levels do not vary among fish types, and we consider whether the levels of any metals could harm the fish themselves or their predators or pose a health risk for human consumers. There were significant interspecific differences for all metals, and no fish types had the highest levels of more than two metals. There were few significant correlations (Kendall tau) among metals for the three most numerous fish (yellowfin tuna, bluefish, and flounder), the correlations were generally low (below 0.40), and many correlations were negative. Only manganese and lead positively were correlated for tuna, bluefish, and flounder. The levels of most metals were below those known to cause adverse effects in the fish themselves. However, the levels of arsenic, lead, mercury, and selenium in some fish were in the range known to cause some sublethal effects in sensitive predatory birds and mammals and in some fish exceeded health-based standards. The greatest risk from different metals resided in different fish; the species of fish with the highest levels of a given metal sometimes exceeded the human health guidance or standards for that metal. Thus, the risk information given to the public (mainly about mercury) does not present a complete picture. The potential of harm from other metals suggests that people not only should eat smaller quantities of fish known to accumulate mercury but also should eat a diversity of fish to avoid consuming unhealthy quantities of other heavy metals. However, consumers should bear in mind that standards have a margin of safety.

Adverse effects of concentrated green tea extracts.

A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Curcumin and cancer: an "old-age" disease with an "age-old" solution.

Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.

Genistein genotoxicity: critical considerations of in vitro exposure dose.

The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundant soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein >5 microM as non-physiological, and thus "high" doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of "the dose defines the poison" applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.

Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powde...

Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to "negative" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)

Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation.

Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.

Poppy seed foods and opiate drug testing--where are we today?

Seeds of the opium poppy plant are legally sold and widely consumed as food. Due to contamination during harvesting, the seeds can contain morphine and other opiate alkaloids. The objective of this study is to review the toxicology of poppy seed foods regarding influence on opiate drug tests. Computer-assisted literature review resulted in 95 identified references. Normal poppy seed consumption is generally regarded as safe. During food processing, the morphine content is considerably reduced (up to 90%). The possibility of false-positive opiate drug tests after poppy food ingestion exists. There are no unambiguous markers available to differentiate poppy food ingestion from heroin or pharmaceutical morphine use. This is also a problem in heroin-assisted maintenance programs. A basic requirement in such substitution programs is the patients' abstinence from any other drugs, including additional illicit heroin. Also a lack of forensic ingestion trials was detected that consider all factors influencing the morphine content in biologic matrices after consumption. Most studies did not control for the losses during food processing, so that the initial morphine dosage was overestimated. The large reduction of the morphine content during past years raises questions about the validity of the "poppy seed defence." However, a threshold of food use that would not lead to positive drug tests with certainty is currently unavailable. Research is needed to prove if the morphine contents in today's foods still pose the possibility of influencing drug tests. Future trials should consider processing-related morphine losses.

Cancer and non-cancer health effects from food contaminant exposures for children and adults in California: a risk assessment

Background In the absence of current cumulative dietary exposure assessments, this analysis was conducted to estimate exposure to multiple dietary contaminants for children, who are more vulnerable to toxic exposure than adults. Methods We estimated exposure to multiple food contaminants based on dietary data from preschool-age children (2–4 years, n=207), school-age children (5–7 years, n=157), parents of young children (n=446), and older adults (n=149). We compared exposure estimates for eleven toxic compounds (acrylamide, arsenic, lead, mercury, chlorpyrifos, permethrin, endosulfan, dieldrin, chlordane, DDE, and dioxin) based on self-reported food frequency data by age group. To determine if cancer and non-cancer benchmark levels were exceeded, chemical levels in food were derived from publicly available databases including the Total Diet Study. Results Cancer benchmark levels were exceeded by all children (100%) for arsenic, dieldrin, DDE, and dioxins. Non-cancer benchmarks were exceeded by >95% of preschool-age children for acrylamide and by 10% of preschool-age children for mercury. Preschool-age children had significantly higher estimated intakes of 6 of 11 compounds compared to school-age children (p<0.0001 to p=0.02). Based on self-reported dietary data, the greatest exposure to pesticides from foods included in this analysis were tomatoes, peaches, apples, peppers, grapes, lettuce, broccoli, strawberries, spinach, dairy, pears, green beans, and celery. Conclusions Dietary strategies to reduce exposure to toxic compounds for which cancer and non-cancer benchmarks are exceeded by children vary by compound. These strategies include consuming organically produced dairy and selected fruits and vegetables to reduce pesticide intake, consuming less animal foods (meat, dairy, and fish) to reduce intake of persistent organic pollutants and metals, and consuming lower quantities of chips, cereal, crackers, and other processed carbohydrate foods to reduce acrylamide intake.

Aluminium and lead: molecular mechanisms of brain toxicity.

The fact that aluminium (Al) and lead (Pb) are both toxic metals to living organisms, including human beings, was discovered a long time ago. Even when Al and Pb can reach and accumulate in almost every organ in the human body, the central nervous system is a particular target of the deleterious effects of both metals. Select human population can be at risk of Al neurotoxicity, and Al is proposed to be involved in the etiology of neurodegenerative diseases. Pb is a widespread environmental hazard, and the neurotoxic effects of Pb are a major public health concern. In spite of the numerous efforts and the accumulating evidence in this area of research, the mechanisms of Al and Pb neurotoxicity are still not completely elucidated. This review will particularly address the involvement of oxidative stress, membrane biophysics alterations, deregulation of cell signaling, and the impairment of neurotransmission as key aspects involved Al and Pb neurotoxicity.

Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity.

The prevalence of allergic-related diseases, food intolerance, and chemical sensitivities in both the pediatric and adult population has increased dramatically over the last two decades, with escalating rates of associated morbidity. Conditions of acquired allergy, food intolerance and chemical hypersensitivity are frequently the direct sequelae of a toxicant induced loss of tolerance (TILT) in response to a significant initiating toxic exposure. Following the primary toxicant insult, the individuals become sensitive to low levels of diverse and unrelated triggers in their environment such as commonly encountered chemical, inhalant or food antigens. Among sensitized individuals, exposure to assorted inciting stimuli may precipitate diverse clinical and/or immune sequelae as may be evidenced by clinical symptoms as well as varied lymphocyte, antibody, or cytokine responses in some cases. Recently recognized as a mechanism of disease development, TILT and resultant sensitivity-related illness (SRI) may involve various organ systems and evoke wide-ranging physical or neuropsychological manifestations. With escalating rates of toxicant exposure and bioaccumulation in the population-at-large, an increasing proportion of contemporary illness is the direct result of TILT and ensuing SRI. Avoidance of triggers will preclude symptoms, and desensitization immunotherapy or immune suppression may ameliorate symptomatology in some cases. Resolution of SRI generally occurs on a gradual basis following the elimination of bioaccumulated toxicity and avoidance of further initiating adverse environmental exposures. As has usually been the case throughout medical history whenever new evidence regarding disease mechanisms emerges, resistance to the translation of knowledge abounds. Copyright © 2010 Elsevier B.V. All rights reserved.

Rye, lignans and human health.

Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

N-Nitroso compounds in the diet.

N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence. Copyright 1999 Elsevier Science B.V.

Developmental and reproductive outcomes in humans and animals after glyphosate exposure: a critical analysis.

Glyphosate is the active ingredient of several widely used herbicide formulations. Glyphosate targets the shikimate metabolic pathway, which is found in plants but not in animals. Despite the relative safety of glyphosate, various adverse developmental and reproductive problems have been alleged as a result of exposure in humans and animals. To assess the developmental and reproductive safety of glyphosate, an analysis of the available literature was conducted. Epidemiological and animal reports, as well as studies on mechanisms of action related to possible developmental and reproductive effects of glyphosate, were reviewed. An evaluation of this database found no consistent effects of glyphosate exposure on reproductive health or the developing offspring. Furthermore, no plausible mechanisms of action for such effects were elucidated. Although toxicity was observed in studies that used glyphosate-based formulations, the data strongly suggest that such effects were due to surfactants present in the formulations and not the direct result of glyphosate exposure. To estimate potential human exposure concentrations to glyphosate as a result of working directly with the herbicide, available biomonitoring data were examined. These data demonstrated extremely low human exposures as a result of normal application practices. Furthermore, the estimated exposure concentrations in humans are >500-fold less than the oral reference dose for glyphosate of 2 mg/kg/d set by the U.S. Environmental Protection Agency (U.S. EPA 1993). In conclusion, the available literature shows no solid evidence linking glyphosate exposure to adverse developmental or reproductive effects at environmentally realistic exposure concentrations.

Perceived risks of conventional and organic produce: pesticides, pathogens, and natural toxins.

Public risk perceptions and demand for safer food are important factors shaping agricultural production practices in the United States. Despite documented food safety concerns, little attempt has been made to elicit consumers' subjective risk judgments for a range of food safety hazards or to identify factors most predictive of perceived food safety risks. In this study, over 700 conventional and organic fresh produce buyers in the Boston area were surveyed for their perceived food safety risks. Survey results showed that consumers perceived relatively high risks associated with the consumption and production of conventionally grown produce compared with other public health hazards. For example, conventional and organic food buyers estimated the median annual fatality rate due to pesticide residues on conventionally grown food to be about 50 per million and 200 per million, respectively, which is similar in magnitude to the annual mortality risk from motor vehicle accidents in the United States. Over 90% of survey respondents also perceived a reduction in pesticide residue risk associated with substituting organically grown produce for conventionally grown produce, and nearly 50% perceived a risk reduction due to natural toxins and microbial pathogens. Multiple regression analyses indicate that only a few factors are consistently predictive of higher risk perceptions, including feelings of distrust toward regulatory agencies and the safety of the food supply. A variety of factors were found to be significant predictors of specific categories of food hazards, suggesting that consumers may view food safety risks as dissimilar from one another. Based on study findings, it is recommended that future agricultural policies and risk communication efforts utilize a comparative risk approach that targets a range of food safety hazards.

Rhabdomyolysis from an intramuscular injection of glyphosate-surfactant herbicide.

INTRODUCTION: Glyphosate-surfactant herbicide (GlySH) is widely used as a non-selective herbicide. Most intoxicated cases are from ingestion, inhalation, and skin exposure. Intramuscular injection of GlySH has never been reported. We present a case of GlySH intoxication via intramuscular injection. CASE REPORT: A 42-year-old woman came to the emergency department complaining of painful swelling of left upper limb for 12 h. She had performed an intramuscular injection of 6 mL of GlySH over the lateral aspect of the left elbow 15 h previously. Physical examination disclosed painful swelling over left distal arm, elbow, and forearm with three needle punctures. CT scan revealed ill-defined areas of heterogeneous high density with marked swelling at subcutaneous tissue over posterior aspect of the elbow. DISCUSSION: The mechanism of toxicity of GlySH is complicated and surfactant was thought to play an important role in GlySH intoxication. Intramuscular GlySH poisoning is different from oral GlySH intoxication. Care should be taken when monitoring acute rhabdomyolysis and compartment syndrome, which may develop rapidly and contribute to the surfactant component of glyphosate formulation.

Toxicological and mutagenic analysis of Artemisia dracunculus (tarragon) extract.

Mutagenicity and liver toxicity of the herb tarragon (Artemisia dracunculus) were evaluated using single cell gel (comet) electrophoresis. Ten microlitres aliquots of peripheral venous human blood were incubated with tarragon extract, saline, or the mutagen sodium dichromate. Cell suspensions dispersed in low-melting agarose were electrophoresed in ethidium bromide. The resulting DNA migration trails were obtained using fluorescent microscopy at 400× magnification, and graded according to the mutagenicity index (MI) for each cell incubation condition. The in vivo liver toxicity of Artemisia dracunculus was assessed in the blood of mice treated orally with the extract of the herb, using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as liver function indicators. Liver morphology was assessed using hematoxylin and eosin (HE) staining of liver tissue. The present study demonstrated a direct correlation between tarragon extract dosage and three major outcome variables: MI; serum liver enzyme activity; and liver histopathology. These outcomes are possibly due to the presence in tarragon of methylchavicol and other genotoxic compounds. These findings provide a preliminary guide for risk assessment of tarragon in diet and in possible therapeutic applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

Exposure to nitrosamines in thirdhand tobacco smoke increases cancer risk in non-smokers.

In addition to passive inhalation, non-smokers, and especially children, are exposed to residual tobacco smoke gases and particles that are deposited to surfaces and dust, known as thirdhand smoke (THS). However, until now the potential cancer risks of this pathway of exposure have been highly uncertain and not considered in public health policy. In this study, we estimate for the first time the potential cancer risk by age group through non-dietary ingestion and dermal exposure to carcinogen N-nitrosamines and tobacco-specific nitrosamines (TSNAs) measured in house dust samples. Using a highly sensitive and selective analytical approach we have determined the presence of nicotine, eight N-nitrosamines and five tobacco-specific nitrosamines in forty-six settled dust samples from homes occupied by both smokers and non-smokers. Using observations of house dust composition, we have estimated the cancer risk by applying the most recent official toxicological information. Calculated cancer risks through exposure to the observed levels of TSNAs at an early life stage (1 to 6years old) exceeded the upper-bound risk recommended by the USEPA in 77% of smokers' and 64% of non-smokers' homes. The maximum risk from exposure to all nitrosamines measured in a smoker occupied home was one excess cancer case per one thousand population exposed. The results presented here highlight the potentially severe long-term consequences of THS exposure, particularly to children, and give strong evidence of its potential health risk and, therefore, they should be considered when developing future environmental and health policies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dietary intake of organotin compounds in Finland: a market-basket study.

The objective of this study was to estimate the intake of organic tin compounds from foodstuffs in a Finnish market basket. The study was conducted by collecting 13 market baskets from supermarkets and market places in the city of Kuopio, eastern Finland. Altogether 115 different food items were bought. In each basket, foodstuffs were mixed in proportion to their consumption and analysed by GC/MS for seven organic tin compounds (mono-, di-, and tributyltin, mono-, di-, and triphenyltin, and dioctyltin). Organotin compounds were detected in only four baskets, with the fish basket containing the largest number of different organotins. The European Food Safety Authority has established a tolerable daily intake of 250 ng kg(-1) body weight for the sum of dibutyltin, tributyltin, triphenyltin and dioctyltin. According to this study, the daily intake of these compounds was 2.47 ng kg(-1) body weight, of which 81% originated from the fish basket. This exposure is only 1% of the tolerable daily intake and poses negligible risk to the average consumer. However, for consumers eating large quantities of fish from contaminated areas, the intake may be much higher.

A survey of feeding N-nitrosodimethylamine (NDMA) to domestic animals over an 18 year period.

Sodium nitrite and formalin have been used as preservatives in the fish meal industry in Norway since 1953. In 1957, fur farms suffered losses of mink due to a new, malignant liver disease. Experimental feeding of herring meal to cows and sheep resulted in the death of some of the animals. Further studies showed that amines (TMAO) normally present in fish, can react with sodium nitrite used as preservative, or nitrogen oxides from the combustion of fuel oils used during processing, to produce the toxic agent, NDMA. Mink and fox may consume considerable amounts of fish meal in their diets. If the fish meal contains sufficient NDMA, the incidence of liver failure or tumours can be quite high. Long-term exposure to as little as 0.1 mg NDMA/kg b.w./day in the diet of mink, cows and sheep can produce fibro-occlusive changes in the hepatic vessels. These lesions can later cause capillary ectasies-like changes in cows, which are similar in appearance to hemangiomas seen in mink. The mink liver hemangiomas develop into hemangiosarcomas. We currently consider capillary ectasies-like changes in cows exposed to NDMA to represent pre-cancerous lesions.

Flatulence--causes, relation to diet and remedies.

In addition to causing embarrassment and unease, flatulence is linked to a variety of symptoms, some of which may be distressing. This review describes the origins of intestinal gas, its composition and methods which have been developed for its analysis. Emphasis is placed upon the effects of legumes in the diet in producing excessive intestinal gas and, particularly, on the role of raffinose-type oligosaccharides, containing alpha-galactosidic groupings. Suggestions for overcoming the problem are presented, including drug treatment, enzyme treatment, food processing and plant breeding. It is emphasised that removal of all raffinose-oligosaccharides from beans does not remove the problem of flatulence in animals and man; the compounds responsible--though assumed to be polysaccharides (or polysaccharide-derived oligomers formed by processing or cooking)--have yet to be characterised.

Organic food: buying more safety or just peace of mind? A critical review of the literature.

Consumer concern over the quality and safety of conventional food has intensified in recent years, and primarily drives the increasing demand for organically grown food, which is perceived as healthier and safer. Relevant scientific evidence, however, is scarce, while anecdotal reports abound. Although there is an urgent need for information related to health benefits and/or hazards of food products of both origins, generalized conclusions remain tentative in the absence of adequate comparative data. Organic fruits and vegetables can be expected to contain fewer agrochemical residues than conventionally grown alternatives; yet, the significance of this difference is questionable, inasmuch as actual levels of contamination in both types of food are generally well below acceptable limits. Also, some leafy, root, and tuber organic vegetables appear to have lower nitrate content compared with conventional ones, but whether or not dietary nitrate indeed constitutes a threat to human health is a matter of debate. On the other hand, no differences can be identified for environmental contaminants (e.g. cadmium and other heavy metals), which are likely to be present in food from both origins. With respect to other food hazards, such as endogenous plant toxins, biological pesticides and pathogenic microorganisms, available evidence is extremely limited preventing generalized statements. Also, results for mycotoxin contamination in cereal crops are variable and inconclusive; hence, no clear picture emerges. It is difficult, therefore, to weigh the risks, but what should be made clear is that 'organic' does not automatically equal 'safe.' Additional studies in this area of research are warranted. At our present state of knowledge, other factors rather than safety aspects seem to speak in favor of organic food.

Heavy metal content of ayurvedic herbal medicine products.

CONTEXT: Lead, mercury, and arsenic intoxication have been associated with the use of Ayurvedic herbal medicine product (HMPs). OBJECTIVES: To determine the prevalence and concentration of heavy metals in Ayurvedic HMPs manufactured in South Asia and sold in Boston-area stores and to compare estimated daily metal ingestion with regulatory standards. DESIGN AND SETTING: Systematic search strategy to identify all stores 20 miles or less from Boston City Hall that sold Ayurvedic HMPs from South Asia by searching online Yellow Pages using the categories markets, supermarkets, and convenience stores, and business names containing the word India, Indian cities, and Indian words. An online national directory of Indian grocery stores, a South Asian community business directory, and a newspaper were also searched. We visited each store and purchased all unique Ayurvedic HMPs between April 25 and October 24, 2003. MAIN OUTCOME MEASURES: Concentrations (microg/g) of lead, mercury, and arsenic in each HMP as measured by x-ray fluorescence spectroscopy. Estimates of daily metal ingestion for adults and children estimated using manufacturers' dosage recommendations with comparisons to US Pharmacopeia and US Environmental Protection Agency regulatory standards. RESULTS: A total of 14 (20%) of 70 HMPs (95% confidence interval, 11%-31%) contained heavy metals: lead (n = 13; median concentration, 40 microg/g; range, 5-37,000), mercury (n = 6; median concentration, 20,225 microg/g; range, 28-104,000), and/or arsenic (n = 6; median concentration, 430 microg/g; range, 37-8130). If taken as recommended by the manufacturers, each of these 14 could result in heavy metal intakes above published regulatory standards. CONCLUSIONS: One of 5 Ayurvedic HMPs produced in South Asia and available in Boston South Asian grocery stores contains potentially harmful levels of lead, mercury, and/or arsenic. Users of Ayurvedic medicine may be at risk for heavy metal toxicity, and testing of Ayurvedic HMPs for toxic heavy metals should be mandatory.

Electric light causes cancer? Surely you're joking, Mr. Stevens.

Night is no longer dark in the modern world, and the Milky Way has disappeared. Electric light has benefits but there are also a few detriments. These are (1) loss of the night sky, (2) wasted energy, (3) harm to animal and plant life, (4) and perhaps increases in some severe human maladies such as cancers of breast and prostate. The science on phototransduction for the circadian system and on clock gene function is evolving rapidly, and it provides a rationale for the idea that circadian disruption from light at night could cause disease. Direct evidence from humans and rodent models has also accumulated to the point where the idea is no longer fanciful. Although it may seem logical now, the journey on the path from electric light to breast cancer has been a tortuous one, at least for me.

Dietary exposure to xenoestrogens in New Zealand.

Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.

Radioprotective effects of Zingiber officinale Roscoe (ginger): past, present and future.

Radiation is an important modality in treating people with cancer especially when surgical intervention is impracticable or might debilitate the patient. However, effective use of ionizing radiation is compromised by the side effects that result from radiation-induced damage to normal tissue. The use of radioprotective compounds, which can selectively protect normal tissues against radiation injury is of immense use because in addition to association with protecting the normal tissue, it will also permits use of higher doses of radiation to obtain better cancer control and possible cure. However, till date no ideal radioprotectors are available as most synthetic compounds are toxic at their optimal concentrations. Plants commonly used as dietary and or therapeutic agents have recently been the focus of attention since in most cases they are non-toxic and are easily accepted for human use. Ginger, the rhizomes of Zingiber officinale Roscoe (Zingiberaceae), has widely been used as both culinary and medicinal agent. Preclinical studies carried out in the last decade has shown that ginger and its phytochemicals dehydrozingerone, zingerone possess radioprotective effects in laboratory animals and in cultured cells in vitro. The hydroalcoholic extract of ginger rhizome when administered either through intraperitoneal or oral route was effective in protecting against gamma radiation-induced sickness and mortality. The phytochemicals dehydrogingerone and zingerone present in ginger are also shown to protect mice against radiation-induced sickness and mortality. Mechanistic studies have indicated that the free radical scavenging, antioxidant affects, anti-inflammatory and anti-clastogenic effects may contribute towards the observed protection. Additionally, studies with tumor bearing mice have also shown that zingerone selectively protects the normal tissues against the tumoricidal effects of radiation. This review for the first time summarizes the results related to the radioprotective properties and also emphasizes the aspects that warrant future research to establish its activity and utility as a radioprotective agent.

Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness.

Harmane, one of the heterocyclic amines (HCAs), is a potent neurotoxin linked to human diseases. Dietary exposure, especially in cooked meats, is the major source of exogenous exposure for humans. However, knowledge of harmane concentrations in cooked meat samples is limited. Our goals were to (1) quantify the concentration of harmane in different types of cooked meat samples, (2) compare its concentration to that of other more well-understood HCAs, and (3) examine the relationship between harmane concentration and level of doneness. Thirty barbecued/grilled meat samples (8 beef steak, 12 hamburger, 10 chicken) were analyzed for harmane and four other HCAs (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine [PhIP], amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [DiMeIQx], and 2-amino-1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine [IFP]). Mean (+/- SD) harmane concentration was 5.63 (+/- 6.63) ng/g; harmane concentration was highest in chicken (8.48 +/- 9.86 ng/g) and lowest in beef steak (3.80 +/- 3.6 ng/g). Harmane concentration was higher than that of the other HCAs and significantly correlated with PhIP concentration. Harmane concentration was associated with meat doneness in samples of cooked beef steak and hamburger, although the correlation between meat doneness and concentration was greater for PhIP than for harmane. Evidence indicates that harmane was detectable in nanograms per gram quantities in cooked meat (especially chicken) and, moreover, was more abundant than other HCAs. There was some correlation between meat doneness and harmane concentration, although this correlation was less robust than that observed for PhIP. Data such as these may be used to improve estimation of human dietary exposure to this neurotoxin.

Do endodontic compounds induce genetic damage? A comprehensive review.

Taking into consideration genetic damage plays an important role in carcinogenesis, the purpose of this paper is to provide an overview on the genotoxic potential of some endodontic compounds currently used in dentistry, such as formocresol, paramonochlorophenol, calcium hydroxide, resin-based sealers, phenolic compounds, chlorhexidine, mineral trioxide aggregate, and others. Some of these compounds appear capable of exerting noxious activity on the genetic material. The action mechanisms are discussed. Therefore, this is an area that warrants investigation since the estimation of risk of these substances with respect to genotoxicity will be added to those used for regulatory purposes in improving oral health and preventing oral carcinogenesis.

Blood Harmane, Blood Lead, and Severity of Hand Tremor: Evidence of Additive Effects

Background Tremor is a widespread phenomenon in human populations. Environmental factors are likely to play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent tremor-producing β-carboline alkaloid. Lead is another tremor-producing neurotoxicant. The effects of harmane and lead with respect to tremor have been studied in isolation. Objectives We tested the hypothesis that tremor would be particularly severe among individuals who had high blood concentrations of both of these toxicants. Methods Blood concentrations of harmane and lead were each quantified in 257 individuals (106 essential tremor cases and 151 controls) enrolled in an environmental epidemiological study. Total tremor score (range = 0 – 36) was a clinical measure of tremor severity. Results The total tremor score ranged from 0 – 36, indicating that a full spectrum of tremor severities was captured in our sample. Blood harmane concentration correlated with total tremor score (p = 0.007), as did blood lead concentration (p = 0.045). The total tremor score was lowest in participants with both low blood harmane and lead concentrations (8.4 ± 8.2), intermediate in participants with high concentrations of either toxicant (10.5 ± 9.8), and highest in participants with high concentrations of both toxicants (13.7 ± 10.4)(p = 0.01). Conclusions Blood harmane and lead concentrations separately correlated with total tremor scores. Participants with high blood concentrations of both toxicants had the highest tremor scores, suggesting an additive effect of these toxicants on tremor severity. Given the very high population prevalence of tremor disorders, identifying environmental determinants is important for primary disease prevention.

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

Comparison of the cytotoxic and mutagenic potential of liquid smoke food flavourings, cigarette smoke condensate and wood smoke condensate.

Although products of pyrolysis are often cytotoxic and mutagenic, the relationship between the type of material pyrolysed and the toxicity of the resulting pyrolysis products is poorly understood. The objective of this study was to evaluate and compare the cytotoxicity and mutagenicity of several types of common pyrolysis products. The cytotoxicity and mutagenicity of these products were assessed by using neutral red uptake and Ames mutagenicity assays, respectively. The biological activities of four liquid smoke food flavourings (LSF) were compared with two other pyrolysis-derived materials; cigarette smoke condensate (CSC) and a wood smoke condensate (WSC). Results indicated all of the mixtures exhibited a concentration-dependent cytotoxic response. The CSC and WSC were less cytotoxic than three of the LSFs, but more cytotoxic than one of the brands. The CSC was mutagenic in two Salmonella strains; however, none of the LSFs or WSC was mutagenic using TA98, and only three of the LSFs were positive with TA100. The six pyrolysis-derived materials evaluated in this study showed differing patterns and magnitudes of cytotoxicity and mutagenicity. These results indicate that the cytotoxicity and mutagenicity of complex mixtures derived from pyrolysis products are affected by the type of material pyrolysed and/or the method used to prepare the mixture. The cytotoxic potential of some commercial smoke flavourings is greater than cigarette smoke condensate and several of the food flavourings are mutagenic in one Salmonella strain.

Reduction of pesticide residues on produce by rinsing.

In 1997 this laboratory initiated a research program with the objective of examining the effect that rinsing of produce with tap water would have on pesticide residues. Samples were obtained from local markets and/or grown at our experimental farm. Because approximately 35% of produce from retail sources contains pesticide residues, growing and treating produce at an experimental farm had the advantage that all such samples contain pesticide residues. Pesticides were applied under normal field conditions to a variety of food crops and the vegetation was allowed to undergo natural weathering prior to harvest. The resulting samples contained field-incurred or "field-fortified" residues. This experimental design was employed to mimic as closely as possible real world samples. Crops were treated, harvested, and divided into equal subsamples. One subsample was processed unwashed, whereas the other was rinsed under tap water. The extraction and analysis method used was a multi-residue method developed in our laboratory. Twelve pesticides were included in this study: the fungicides captan, chlorothalonil, iprodione, and vinclozolin; and the insecticides endosulfan, permethrin, methoxychlor, malathion, diazinon, chlorpyrifos, bifenthrin, and DDE (a soil metabolite of DDT). Statistical analysis of the data using the Wilcoxon signed-rank test showed that rinsing removed residues for nine of the twelve pesticides studied. Residues of vinclozolin, bifenthrin, and chlorpyrifos were not reduced. The rinsability of a pesticide is not correlated with its water solubility.

Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas.

Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.

The immunobiology of mushrooms.

There has been enormous interest in the biologic activity of mushrooms and innumerable claims have been made that mushrooms have beneficial effects on immune function with subsequent implications for inhibition of tumor growth. The majority of these observations are anecdotal and often lack standardization. However, there remains considerable data on both in vitro and in vivo effects that reflect on the potential of mushroom compounds to influence human immunity. A number of these effects are beneficial but, unfortunately, many responses are still characterized based on phenomenology and there is more speculation than substance. With respect to tumor biology, although many neoplastic lesions are immunogenic, tumor antigens frequently are self antigens and induce tolerance and many patients with cancer exhibit suppressed immune responses, including defective antigen presentation. Therefore, if and when mushroom extracts are effective, they more likely function as a result of improved antigen presentation by dendritic cells than by a direct cytopathic effect. In this review we attempt to place these data in perspective, with a particular focus on dendritic cell populations and the ability of mushroom extracts to modulate immunity. There is, at present, no scientific basis for the use of either mushrooms or mushroom extracts in the treatment of human patients but there is significant potential for rigorous research to understand the potential of mushrooms in human disease and thence to focus on appropriate clinical trials to demonstrate effectiveness and/ or potential toxicity.

Short- and long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident".

The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.

Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms.

The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.

Genotoxicity of lavender oil, linalyl acetate, and linalool on human lymphocytes in vitro.

The potential genotoxicity of lavender essential oil and its major components, linalool, and linalyl acetate, was evaluated in vitro by the micronucleus test on peripheral human lymphocytes. In the range of non-toxic concentrations (0.5-100 μg/ml), linalyl acetate increased the frequency of micronuclei significantly and in concentration-dependent manner; lavender oil did so only at the highest concentration tested, whereas linalool was devoid of genotoxicity. None of the tested substances led to an increase in nucleoplasmic bridges or nuclear buds frequency. These findings suggest that the mutagenic activity of lavender oil can be related to the presence of linalyl acetate, which seems to have a profile of an aneugenic agent. Copyright © 2010 Wiley-Liss, Inc.

Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates.

Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.

Antimutagens and anticarcinogens: a survey of putative interceptor molecules.

In this review recent publications are cited for a number of antimutagens. The molecules surveyed are potential or proven "desmutagens" or "interceptors." These are biologically prevalent or synthetic molecules that are most often small metabolites proficient in binding to, or reacting with, mutagenic chemicals and free radicals. Many of this class of "blocking agents" are "soft" and "hard" nucleophiles with consequently varying abilities to react with particular classes of electrophiles, the major classes of direct-acting mutagens. Although they serve as a first line of defense against mutagens and carcinogens, many interceptor molecules are under-investigated with regard to their spectra of activity and their possible relevance to prophylaxis or treatment of human disease states.

Commercial hickory-smoke flavouring is a human lymphoblast mutagen but does not induce lung adenomas in newborn mice.

Commercial aqueous wood-smoke flavouring induced significant increases in the 6-thioguanine resistance mutation frequency of TK6 human lymphoblasts at 0.1 microliter flavouring/ml of cell suspension. This corresponds to 6 micrograms/ml of dissolved 'solids' as determined by fully drying the aqueous flavouring in a vacuum desiccator. In AHH-1 human lymphoblasts, which contain a cytochrome P-450 monooxygenase system, mutations were induced at 0.3 microliter/ml, corresponding to 18 microliters/ml of dissolved 'solids'. The flavouring did not induce 8-azaguanine resistant mutations in Salmonella typhimurium at concentrations up to 1.5 microliter/ml. At higher concentrations the flavouring was toxic to bacteria. The flavouring did not induce lung adenomas or other tumours in newborn mice when injected ip with total doses of up to 26 microliters over a 3-wk period. Toxicity to the kidney, colon and rectum was observed in some mice at 15 wk of age.

Quantification of the co-mutagenic beta-carbolines, norharman and harman, in cigarette smoke condensates and cooked foods.

Co-mutagenic beta-carbolines, such as norharman and harman, were quantified in mainstream and sidestream smoke condensates of six Japanese brands of cigarettes, and also in 13 kinds of cooked foods, using a combination of blue cotton treatment and HPLC. Norharman and harman were detected in all the cigarette smoke condensate samples. Their levels in the mainstream smoke case were 900-4240 ng per cigarette for norharman, and 360-2240 ng for harman, and in sidestream smoke, 4130-8990 ng for norharman and 2100-3000 ng for harman. These beta-carbolines were also found to be present in all the cooked food samples, at levels of 2.39-795 ng for norharman and 0.62-377 ng for harman per gram of cooked food. The observed concentrations are much higher than those found for mutagenic and carcinogenic heterocyclic amines (HCAs), suggesting that humans are exposed to norharman and harman in daily life to a larger extent than to HCAs.

The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease.

It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing. Something in our environment associated with development is poisoning the minds of our aged. The epidemic is associated with the use of copper plumbing, and the taking of copper in multi-mineral supplements. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier. I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population.

In vitro binding capacities of three dietary fibers and their mixture for four toxic elements, cholesterol, and bile acid.

Water-soluble dietary fibers from apple peels and water-insoluble dietary fibers from wheat bran and soybean-seed hull were used to evaluate their binding capacities for four toxic elements (Pb, Hg, Cd, and As), lard, cholesterol, and bile acids. The water-soluble dietary fibers showed a higher binding capacity for three toxic cations, cholesterol, and sodium cholate; and a lower binding capacity for lard, compared to the water-insoluble ones. A mixture of the dietary fibers from all samples - apple peels, wheat bran, and soybean-seed hull - in the ratio 2:4:4 (w/w) significantly increased the binding capacity of water-insoluble dietary fibers for the three toxic cations, cholesterol, and sodium cholate; moreover, the mixture could lower the concentrations of Pb(2+) and Cd(+) in the tested solutions to levels lower than those occurring in rice and vegetables grown in polluted soils. However, all the tested fibers showed a low binding capacity for the toxic anion, AsO(3)(3-). Copyright © 2010. Published by Elsevier B.V.