Acute poisonings treated in hospitals in Oslo: a one-year prospective study (I): pattern of poisoning.

OBJECTIVES: Prospective design is mandatory to study pattern of poisoning and suicidal intention of patients. MATERIAL AND METHODS: Prospective cross-sectional multi-center study of all patients contacting health care services because of acute poisoning during one year in Oslo, irrespective of intention. Data on the adult hospitalized patients (> or = 16 years) are presented here. RESULTS: Of a total of 3,775 such adult contacts (3,025 episodes), there were 947 (31 %) hospitalizations; annual incidence 1.9 (per 1,000) in males and 2.1 in females. Median age was 36 years (range 16-89); 54% females. Benzodiazepines (18%), ethanol (17%), paracetamol (12%), opioids (7%), and gamma hydroxybutyric acid (GHB) (7%) were most frequently taken. Patients stated suicidal intention in 29% of the admissions; physicians in 10%. CONCLUSION: Benzodiazepines and ethanol were the most common agents, but newer illicit drugs were frequent, especially GHB. Males often took ethanol and drugs of abuse; females often used prescription drugs with suicidal intention.

Liquid chromatography-tandem mass spectrometry analysis of 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine in cooked meats.

Several cooked meats such as beef (fried, coated-fried), pork (fried, coated-fried), and chicken (fried, griddled, coated-fried, roasted) were analyzed for the heterocyclic amine 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5- b]pyridine (4'-OH-PhIP) not commonly determined in food and 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP). The highest content of 4'-OH-PhIP was found in fried and griddled chicken breast, the concentration being 43.7 and 13.4 ng/g, respectively, whereas the corresponding PhIP concentrations were 19.2 and 5.8 ng/g. The estimated concentration of both pyridines in fried pork loin, in fried pork sausages, and in coated-fried chicken was below 2.5 ng/g. In the rest of the samples, 4'-OH-PhIP was not detected. The analyses were performed by solid-phase extraction and LC-MS/MS. The fragmentation of 4'-OH-PhIP in an ion trap mass analyzer was studied in order to provide information for the identification of 4'-OH-PhIP. Additionally, the effect of red wine marinades on the formation of 4'-OH-PhIP in fried chicken was examined, finding a notable reduction (69%) in the amine's occurrence.

Dietary intake of heterocyclic amines in relation to socio-economic, lifestyle and other dietary factors: estimates in a Swedish population.

OBJECTIVES: To estimate the dietary intakes of heterocyclic amines (HCAs), to examine the intakes in relation to socio-economics, lifestyle and other dietary factors and to compare the classification of subjects by intake of HCA versus intake of meat and fish. DESIGN: Cross-sectional analysis within the Malmö Diet and Cancer (MDC) cohort. Data were obtained from a modified diet history, a structured questionnaire on socio-economics and lifestyle, anthropometric measurements and chemical analysis of HCAs. HCA intake was cross-classified against meat and fish intake. The likelihood of being a high consumer of HCAs was estimated by logistic regression analysis. Dietary intakes were examined across quintiles of HCA intake using analysis of variance. SETTING: Baseline examinations conducted in 1991-1994 in Malmö, Sweden. SUBJECTS: A sub-sample of 8599 women and 6575 men of the MDC cohort. RESULTS: The mean daily HCA intake was 583 ng for women and 821 ng for men. Subjects were ranked differently with respect to HCA intake compared with intake of fried and baked meat and fish (kappa = 0.13). High HCA intake was significantly associated with lower age, overweight, sedentary lifestyle and smoking. Intakes of dietary fibre, fruits and fermented milk products were negatively associated with HCA intake, while intakes of selenium, vegetables, potatoes, alcohol (among men) and non-milk-based margarines (among women) were positively associated with HCA intake. CONCLUSIONS: The estimated daily HCA intake of 690 ng is similar to values obtained elsewhere. The present study suggests that lifestyle factors (e.g. smoking, physical activity, fruit and vegetable intakes, and types of milk products and margarines) may confound associations between HCA intake and disease. The poor correlation between HCA intake and intakes of fried meat and fish facilitates an isolation of the health effects of HCAs.

Canavanine content in sword beans (Canavalia gladiata): analysis and effect of processing.

The amino acid canavanine is a potentially toxic constituent of leguminous seeds. The aim of the present study was to determine the ability of different processing methods to reduce canavanine in sword beans (Canavalia gladiata). For this purpose a method for the detection and quantification of canavanine was developed using reversed-phase high-performance liquid chromatography of the dabsylated derivatives. The recovery of canavanine using this method was 88-91%. Optimum extraction of canavanine from raw and processed beans was obtained by addition of hot water prior to overnight soaking. The results obtained with this method agree well with previously published values for raw seeds. The method is sensitive, specific and can successfully be applied to the detection of canavanine in legumes. Overnight soaking and boiling in excess water followed by decanting gave the most pronounced reduction in canavanine content (around 50%), followed by boiling and decanting excess water (34%). Roasting as used in this study and autoclaving were less effective in reducing the canavanine content.

Analysis of heterocyclic amines in food products: interlaboratory studies.

A feasibility study and two interlaboratory exercises on the determination of selected heterocyclic amines (HAs) in beef extract, organised in the framework of a European project, are presented. The aim of these exercises was to improve the quality of the laboratories and to evaluate the performance of a standardised analytical method and also the methods currently used by each of the participants for the analysis of these compounds. Three lyophilised portions of a commercial beef material previously spiked with HAs at different concentration levels ranging from 10 to 75 ng g(-1) were used as laboratory reference materials (lot A, B and C). Firstly, a feasibility study was carried out using a test standard solution and the beef extract (lot A), which contained only five HAs. Then, two interlaboratory exercises were carried out using the laboratory reference materials lot B and lot C, containing 10 selected HAs at two different concentration levels, 75 and 10 ng/g, respectively. The results obtained by all participant laboratories using the proposed method showed satisfactory agreement and the CV(%) between-laboratories obtained were from 8.3 to 24.1% for lot B and from 8.7 to 44.5% for lot C. The standardised method evaluated in these collaborative studies is therefore proposed for the analysis of HAs in food material. Moreover, LC-MS is recommended as the most suitable technique for the analysis of a large number of HAs in food 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.

Long-term retention of neurotoxic beta-carbolines in brain neuromelanin.

beta-Carbolines show structural resemblance to the neurotoxic N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and are metabolized to mitochondrial toxicants. Humans are continuously exposed to low levels of beta-carbolines through cooked food, coffee, alcoholic beverages and tobacco smoke. beta-Carbolines have previously been detected in higher levels in the pigmented substantia nigra than in the cortex of humans. The distribution of 3H-labelled harman and norharman in the brain of pigmented and albino mice and in frogs (a species having neuromelanin) was studied by tape-section and light-microscopic autoradiography. Furthermore, the binding of these beta-carbolines to dopamine-melanin and melanin granules from Sepia officinalis was examined. The results revealed a high affinity binding to melanin and a long-term retention (up to 30 days) in pigmented tissues, including neuromelanin-containing neurons of frogs after a single injection. The role of long-term exposure to food-related beta-carbolines and a retention of these compounds in pigment-containing neurons in the induction of idiopathic Parkinson's disease should be further considered.

Influence of antioxidants in virgin olive oil on the formation of heterocyclic amines in fried beefburgers.

An association between the intake of heterocyclic amines (HAs) and the development of cancer has been observed in some epidemiological studies, while in other studies no such correlation has been found. HAs are mutagenic/carcinogenic compounds formed at low levels via the Maillard reaction and a free radical mechanism during cooking of animal tissue. The addition of pure antioxidants or foods containing antioxidants has previously been shown to decrease the amount of HAs formed during cooking. In this study, beefburgers were fried in six different oils: refined olive oil, virgin olive oil, virgin olive oil depleted of phenols, rapeseed oil, virgin olive oil with rosemary extract and refined olive oil with rosemary extract. The content of antioxidative compounds in the virgin olive oil and the rosemary extract was determined. The beefburgers were analysed with regards to 12 different HAs by solid phase extraction and HPLC analysis. MeIQx, 4,8-DiMeIQx, PhIP, Harman and Norharman were detected in all beefburgers fried in the different oils, but the relative amounts varied. Frying in virgin olive oil reduced the formation of HAs compared with refined olive oil. This effect is probably due to the content of phenols in the virgin olive oil. The HA-reducing effect of virgin olive oil decreased during storage, but the addition of rosemary extract may prevent this decrease.

Problems associated with the determination of heterocyclic amines in cooked foods and human exposure.

Epidemiological studies have shown diet to be an important factor in the global variation of human cancer rates. The presence of mutagenic/carcinogenic heterocyclic aromatic amines (HAs) in cooked foods has attracted a great deal of interest for more than 20 years. Accurate assessment of the human exposure to HAs requires food questionnaires that address cooking methods and reliable methods for the analysis of HAs in cooked foods, and of biomarkers of exposure. The complex food matrix, the low amounts of HAs present (ng/g), and the need for several isolation steps make accurate quantification difficult. Food composition, for example the concentrations and relative amounts of naturally occurring precursors, such as creatine, free amino acids and sugars and also the presence of enhancing or inhibiting compounds are known to greatly influence the formation of HAs. Cooking temperature and time are other important factors that affect the yield of HAs. One of the most abundant HAs, PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine), is found typically in amounts up to around 35 ng/g, but there are some reports on much higher levels of PhIP. The levels of other HAs such as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and IFP (2-amino-1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine) generally range from not detectable up to 10 ng/g, and AalphaC (2-amino-9H-pyrido[2,3-b]indole) up to 20 ng/g. Among the factors that influence human exposure to HAs are the type of food, cooking method, portion size and intake frequency. The estimated daily intake of HAs in different studies ranges from 0 to around 15 microg per person per day.

Heterocyclic amines in poultry products: a literature review.

Health risks associated with heterocyclic amines in cooked foods have been discussed and analysed since the presence of these food mutagens was first detected. Intake, metabolism, carcinogenicity and epidemiology are important parameters in the risk assessment of heterocyclic amines. It is very difficult to determine the human intake of heterocyclic amines, as the content in cooked meat is highly dependent on the type of meat and how it has been prepared. This review summarises data on estimates of the content of heterocyclic amines in heat-treated poultry products.

Screening for heterocyclic amines in chicken cooked in various ways.

Chicken cooked under well-controlled conditions and commercial chicken products were screened for heterocyclic amines (HAs). Chicken samples were boiled, deep-fried, pan-fried, oven-roasted, cooked in an unglazed clay pot or in a roasting bag in the oven, and oven broiled. 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 1-methyl-9H-pyrido[3,4-b]indole (harman) and 9H-pyrido[3,4-b]indole (norharman) were identified in several samples. Chicken cooked at low temperatures contained low amounts of HAs. In pan-fried chicken breasts, MeIQx was detected in amounts below 2 ng/g, 4,8-DiMeIQx below 0.6 ng/g, and PhIP in amounts up to 38 ng/g. Harman and norharman were detected in almost all samples (below 15 ng/g). In skin from a commercially barbecued chicken, MeIQx, 4,8-DiMeIQx and PhIP were detected, while only traces of MeIQx were detected in the meat. MeIQx was detected in a commercial chicken flavour, 0.1 ng/ml. No HAs were detected in pan-fried chicken liver. The results show that the content of HAs in chicken cooked in various ways is low if prepared at low temperatures, and increases with increasing cooking temperature. PhIP formation seems to start accelerating at cooking temperatures around or above 200 degrees C. Colour development increases with cooking temperature, but no correlation with HA content was observed.

Characterization of phenolic compounds in virgin olive oil and their effect on the formation of carcinogenic/mutagenic heterocyclic amines in a model system.

Mutagenic heterocyclic amines (HAs) are formed at low levels during cooking of meat and fish, and some of them are considered to be possible human carcinogens. The formation of HAs may be affected by the presence of synthetic or naturally occurring antioxidants. In the present study the effect of virgin olive oil (VOO) phenolic compounds, identified and quantified by LC-MS, on the formation of HAs in a model system was evaluated. An aqueous solution of creatinine, glucose, and glycine was heated in the presence of two samples of VOO differing only in the composition of phenolic compounds. The addition of VOO to the model system inhibited the formation of 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) by between 30 and 50% compared with the control. Fresh-made olive oil, which contained a high amount of dihydroxyphenylethanol derivatives, inhibited HA formation more than a 1-year-old oil did. The inhibition of HA formation was also verified using phenolic compounds extracted from VOO.

Heterocyclic amines: human carcinogens in cooked food?

During the frying of meat and fish, genotoxic heterocyclic amines (HCAs) are formed. The dietary exposure to HCAs may be implicated in the aetiology of human cancer, but there may be other factors in our diet that prevent the genotoxic effects of these compounds. Within the project described here, we plan to identify regional and individual cooking habits that affect HCA-levels in our food. These are determined with a validated analytical method and the exposure to HCAs is estimated by dietary assessment. Biomarker analysis will be employed to estimate recent or long-term exposure to HCAs. In order to identify genetically determined risk factors in humans, cell lines are genetically engineered expressing allelic variants of acetyl- and sulfotransferases implicated in HCA metabolism. Species differences of metabolism and toxicity of HCAs are assessed and the influence of the intestinal microflora on HCA-induced toxicity is evaluated. Dietary constituents that may reduce the genotoxicity of HCAs are screened for potential protective effects in in vitro and in vivo model systems. Finally, we will aim at human intervention studies to investigate if these protective factors are relevant for man. The objectives of this project are to estimate and possibly reduce the exposure levels to HCAs in Europe, to identify populations highly susceptible to HCA toxicity, and to reduce the toxic effects of HCAs by protective factors.

Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study.

BACKGROUND: Heterocyclic amines formed in cooked meat and fish are carcinogenic in animal models and form DNA adducts in human beings. We undertook a study to assess whether these substances are related to the risks of cancer in the large bowel and urinary tract. METHODS: In a population-based case-control study, cases were identified from the Swedish cancer registry. Controls were randomly selected from the population register. Information on intake of various foods and nutrients was assessed by questionnaire, with photographs of foods cooked at various temperatures. We measured the content of heterocyclic amines in foods cooked under these conditions. FINDINGS: Information was retrieved from 553 controls, 352 cases of colon cancer, 249 cases of rectal cancer, 273 cases of bladder cancer, and 138 cases of kidney cancer. The response rate was 80% for controls and 70% for cases. The estimated daily median intake of heterocyclic amines was 77 ng for controls, and 66 ng, 63 ng, 96 ng, and 84 ng for cases with cancer of the colon, rectum, bladder, and kidney, respectively. The relative risk for the intake of heterocyclic amines (highest vs lowest quintile) was 0.6 (95% CI 0.4-1.0) for colon cancer, 0.7 (0.4-1.1) for rectal cancer, 1.2 (0.7-2.1) for bladder cancer, and 1.0 (0.5-1.9) for kidney cancer. Seven cases, but no controls, had an estimated daily intake of heterocyclic amines above 1900 ng. INTERPRETATION: Intake of heterocyclic amines, within the usual dietary range in this study population, is unlikely to increase the incidence of cancer in the colon, rectum, bladder, or kidney. For daily intakes above 1900 ng, our data are consistent with human carcinogenicity, but the precision was extremely low.

Heterocyclic amines in process flavours, process flavour ingredients, bouillon concentrates and a pan residue.

Seven process flavours, five process flavour ingredients, four bouillon concentrates and a pan residue were analysed for mutagenic/carcinogenic heterocyclic amines. To improve chromatographic efficiency for samples with complex matrixes (process flavours, pan residues, etc.), a new additional purification method was designed. The following polar heterocyclic amines were detected: 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in one sample (3.4 ng/g), 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx) in two samples (0.7-2.0 ng/g), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in four samples (1.0-13.8 ng/g), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) in three samples (1.3-2.9 ng/g), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx) in one sample (0.3 ng/g), and traces of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in two samples. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) was not identified in any of the samples. The following non-polar heterocyclic amines were detected: 2-amino-9H-pyrido[2,3-b]indole (AalphaC) in one sample (0.4 ng/g), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) in one sample (20.3 ng/g), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in two samples (1.4-1.7 ng/g), and traces of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in two samples. Of the co-mutagenic heterocyclic amines, 1-methyl-9H-pyrido[3,4-b]indole (harman) was identified in 15 of 17 samples (3.3-755 ng/g), and 9H-pyrido[3,4-b]indole (norharman) in 16 of 17 samples (1.2-176 ng/g). The polar heterocyclic amines were detected only in the samples of animal and mixed animal plus vegetable origin, while the non-polar heterocyclic amines were identified in samples of animal, mixed animal plus vegetable and pure vegetable origin.

Inhibitory effect of threo-9,10-dichlorostearic acid on the mutagenic activity of MeIQx, 2-AF and B[a]P in the Ames/Salmonella test.

The mutagenic activity of threo-9,10-dichlorostearic acid, one of the chlorinated fatty acids identified in fish lipids, was examined in the Ames/Salmonella test. No mutagenic activity was found on any of the Salmonella typhimurium strains TA 98, TA 100 and TA 102, either with or without S9 activation. On the other hand, dichlorostearic acid showed an inhibitory effect on the mutagenic activity of the indirectly-acting mutagens 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-aminofluorene (2-AF) and benzo[a]pyrene (B[a]P) using strain TA 98 in the presence of S9. However, no inhibition was observed when mixing MeIQx and S9 before the addition of dichlorostearic acid. Furthermore, dichlorostearic acid did not show any inhibitory effect on the mutagenic activity of the directly-acting mutagen 4-nitroquinoline-N-oxide (4NQO) using the tester strains TA 98 and TA 100. We, therefore, suggest that dichlorostearic acid interacts with the enzymes of the S9 mix, thereby dose-dependently inhibiting the transformation of MeIQx, 2-AF and B[a]P into their active forms.

Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake.

Frying or grilling of meat and fish products may generate low ppb levels of mutagenic/carcinogenic heterocyclic amines (HAs). Many heterocyclic amines are formed via the Maillard reaction from creatine, free amino acids and monosaccharides; compounds naturally occurring in protein-rich foods of animal origin. The formation and yield of HAs are dependent on physical parameters, such as cooking temperature and time, cooking technique and equipment, heat and mass transport, and on chemical parameters, especially the precursors to HAs. This paper reviews the current knowledge on the formation of HAs in cooked foods and model systems, and summarizes data on the content of HAs in various cooked foods, and estimates of the dietary intake of HAs. It should be noted that the presence of carcinogens of other types in food (e.g. nitrosamines, aromatic amines, cholesterol oxide products) and that their generation during frying and grilling are outside the scope of this review.

Analysis of nonpolar heterocyclic amines in cooked foods and meat extracts using gas chromatography-mass spectrometry.

Heat processing of muscle foods gives rise to the formation of mutagenic and carcinogenic heterocyclic amines, often at ng/g levels. A gas chromatographic-mass spectrometric (GC-MS) technique was introduced for the analysis of nonpolar heterocyclic amines in common cooked meats, pan residues, and meat extracts after solid-phase extraction. The mutagenic heterocyclic amines 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-9H-pyrido[2,3-b]indole (A alpha C) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) were identified in several samples in amounts up to 8 ng/g. Also the comutagenic substances 1-methyl-9H-pyrido [3,4-b]indole (harman) and 9H-pyrido[3,4-b]indole (norharman) were detected in the samples in amounts up to almost 200 ng/g. The GC-MS method can be applied without derivatisation of the sample. The technique offers high chromatographic efficiency, yielding detection limits for pure references in the range 0.1-2 ng per injection.

Assessment of the human exposure to heterocyclic amines.

Heterocyclic amines are possible human carcinogens and fried meat is an important source of exposure in the Western diet. To study the effect of heterocyclic amines in humans, accurate assessment of individual food consumption is essential. Parameters influencing the intake include the amount and type of meat ingested, frequency of consumption, cooking method, cooking temperature and the duration of cooking. The aim of the present study was to develop a practical method for assessing individual intakes of specific heterocyclic amines in a large sample of people. This has been done by combining information on food consumption and laboratory findings of heterocyclic amines in food products. Diet was assessed using a semi-quantitative food frequency questionnaire including photos of fried meat and, in all, 22 dishes were cooked and chemically analyzed. The method was employed in an elderly population in Stockholm to estimate the daily mean intake of the five heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The total daily intake ranged from none to 1816 ng, with a mean intake of 160 ng, which is well below estimates reported previously. Highest amounts ingested were of PhIP (mean 72, range 0-865 ng/day) and MeIQx (mean 72, range 0-1388 ng/day), followed by DiMeIQx (mean 16, range 0-171 ng/day), while MeIQ and IQ were ingested only in very small amounts (mean <1 ng/day).

Trigonelline, a naturally occurring constituent of green coffee beans behind the mutagenic activity of roasted coffee?

Trigonelline and amino acids are natural components in green coffee beans. Model systems mimicking coffee roasting were used to produce heated samples of trigonelline, amino acids and glucose. Trigonelline and amino acids were heated separately or in combinations for 20 min at 250 degrees C. The results of bacteria mutation assays (Salmonella typhimurium strains TA 98, YG 1024 and YG 1029) showed that trigonelline, alone or in combination with most of the single amino acids and mixtures of amino acids, yielded potent mutagenic activity. Of the singly heated compounds, the highest mutagenic activity was found for trigonelline. The mutagenic activity detected with metabolic activation of the heated trigonelline samples indicated that the mutagenic compounds might be amines; however, higher mutagenic activity was found for trigonelline and its combinations without metabolic activation, which suggests that other types of mutagens (direct-acting) were predominant. High-performance liquid chromatographic analysis of some of the heated samples did not reveal the presence of any known mutagenic heterocyclic amine.