Functional and proliferative effects of repeated low‐dose oral administration of furan in rat liver

Scope: Furan, a food contaminant formed during heat processing, induces hepatocellular tumors in rodents and high incidences of cholangiocarcinomas in rats even at the lowest dose (2 mg/kg b.w.) administered. Initial estimates suggested that human intake of furan may be as high as 3.5 μg/kg b.w./day, indicating a relatively narrow margin of exposure. The aim of this study was to establish dose–response data for cytotoxicity, regenerative cell proliferation and secondary oxidative DNA damage in livers of male F344 rats treated with furan at doses ≤2 mg/kg b.w. for 28 days. Methods and results: No significant signs of hepatotoxicity other than a mild, dose‐dependent increase in serum cholesterol and unconjugated bile acids, and no evidence of oxidative DNA damage were seen. Histopathological alterations and proliferative changes were restricted to subcapsular areas of the left and caudate liver lobes. Conclusion: Although statistically significant effects were only seen at the 2 mg/kg b.w. dose during the course of our study, a ～two and ～threefold increase in 5‐bromo‐2′‐deoxyuridine labeling index was observed at 0.1 and 0.5 mg/kg b.w., respectively, suggesting that chronic exposure to doses even below 2 mg/kg b.w. may cause proliferative changes in rat liver and highlighting the need to assess furan carcinogenicity at lower doses.     

A comprehensive review of furan in foods: From dietary exposures and in vivo metabolism to mitigation measures

Furan is a thermal food processing contaminant that is ubiquitous in various food products such as coffee, canned and jarred foods, and cereals. A comprehensive summary of research progress on furan is presented in this review, including discussion of (i) formation pathways, (ii) occurrence and dietary exposures, (iii) analytical techniques, (iv) toxicities, (v) metabolism and metabolites, (vi) risk assessment, (vii) potential biomarkers, and (viii) mitigation measures. Dietary exposure to furan varies among different countries and age groups. Furan acts through various toxicological pathways mediated by its primary metabolite, cis-2-butene-1,4-dial (BDA). BDA can readily react with glutathione, amino acids, biogenic amines, or nucleotides to form corresponding metabolites, some of which have been proposed as potential biomarkers of exposure to furan. Present risk assessment of furan mainly employed the margin of exposure approach. Given the widespread occurrence of furan in foods and its harmful health effects, mitigating furan levels in foods or exploring potential dietary supplements to protect against furan toxicity is necessary for the benefit of food safety and public health.     

Formation of furan in baby food products: Identification and technical challenges

Furan is generally produced during thermal processing of various foods including baked, fried, and roasted food items such as cereal products, coffee, canned, and jarred prepared foods as well as in baby foods. Furan is a toxic and carcinogenic compound to humans and may be a vital hazard to infants and babies. Furan could be formed in foods through thermal degradation of carbohydrates, dissociation of amino acids, and oxidation of polyunsaturated fatty acids. The detection of furan in food products is difficult due to its high volatility and low molecular weight. Headspace solid-phase microextraction coupled with gas chromatography/mass spectrometer (GC/MS) is generally used for analysis of furan in food samples. The risk assessment of furan can be characterized using margin of exposure approach (MOE). Conventional strategies including cooking in open vessels, reheating of commercially processed foods with stirring, and physical removal using vacuum treatment have remained unsuccessful for the removal of furan due to the complex production mechanisms and possible precursors of furan. The innovative food-processing technologies such as high-pressure processing (HPP), high-pressure thermal sterilization (HPTS), and Ohmic heating have been adapted for the reduction of furan levels in baby foods. But in recent years, only HPP has gained interest due to successful reduction of furan because of its nonthermal mechanism. HPP-treated baby food products are commercially available from different food companies. This review summarizes the mechanism involved in the formation of furan in foods, its toxicity, and identification in infant foods and presents a solution for limiting its formation, occurrence, and retention using novel strategies.     

Estimation of long-term dietary exposure to acrylamide of the Japanese people

Acrylamide is a probable human carcinogen and known human neurotoxin. This study estimated hypothetical long-term dietary exposure to acrylamide of the Japanese people using probabilistic and deterministic approaches by combining the concentration of acrylamide in foods with the amount and frequency of food consumption in the population. Data included acrylamide concentrations in more than 2400 individual food samples from a national survey and the literature from 2004 to 2013. Food consumption amounts were derived from the data of 24,293 Japanese citizens aged 1 year and older in the 2012 National Health and Nutrition Survey. Median lifetime average dietary exposure to acrylamide was estimated as 147–154 ng/kg body weight (bw)/day (95th percentile, 226–261 ng/kg bw/day). The deterministic estimate of lifetime exposure was 158 ng/kg bw/day and ranged from 119 ng/kg bw/day for the period of life after 60 years old to 409 ng/kg bw/day for the period between 1 and 6 years old. This study found that vegetables cooked at a high temperature, coffee and cooked potato were the major food groups contributing to long-term dietary acrylamide exposure of the Japanese people.     

Survey of furan in heat processed foods by headspace gas chromatography/mass spectrometry and estimated adult exposure

Furan is a suspected human carcinogen that is formed in some processed foods at low ng per g levels. Recent improvements in analytical methodology and scientific instrumentation have made it possible to accurately measure the amount of furan in a wide variety of foods. Results from analysis of more than 300 processed foods are presented. Furan was found at levels ranging from non-detectable (LOD, 0.2-0.9 ng g^-1) to over 100 ng g^-1. Exposure estimates for several adult food types were calculated, with brewed coffee being the major source of furan in the adult diet (0.15 µg kg^-1 body weight day^-1). Estimates of mean exposure to furan for different subpopulations were calculated. For consumers 2 years and older, the intake is estimated to be about 0.2 µg kg^-1 body weight day^-1.     

Furan and Methylfurans in Foods: An Update on Occurrence,Mitigation, and Risk Assessment

The acceptance of many foods is related to traditional cooking practices, which create taste and texture and are important to digestibility, preservation, and the reduction of foodborne illnesses. A wide range of compounds are formed during the cooking of foods, a number of these have been shown to lead to adverse effects in classical toxicological models and are known as food processing contaminants (FPC). It is essential that the presence and effects of such compounds alone and in combination within the diet are understood such that proportionate risk management measures can be developed, while taking a holistic view across the whole value chain. Furan and alkylfurans (principally 2‐ and 3‐methylfuran) are highly volatile FPC, which are formed in a wide range of foods at low amounts. The focus of research to‐date has been on those foods, which have been identified to be most consequential in terms of being sources of exposure, namely jarred and canned foods for infants and young children (meals and drinks) and coffee (roast and ground, soluble). This report presents (i) new industry data on the occurrence of furan and methylfurans in selected food categories following previous coffee studies, (ii) the most salient parameters that impact furan formation, and (iii) aspects of importance for the risk assessment.     

Analysis of furan in heat-processed foods consumed in Korea using solid phase microextraction–gas chromatography/mass spectrometry (SPME–GC/MS)

Furan (C₄H₄O) is a volatile compound formed during the Maillard reaction and was recently classified as a possible human carcinogen (group 2B) by the International Agency for Research on Cancer. It has been reported to occur in various canned and jarred foods that undergo heat treatment. The aim of the present study was to optimise the sample preparation for furan analysis using solid phase microextraction–gas chromatography/mass spectrometry (SPME–GC/MS), according to the food matrix. We also performed the monitoring and risk assessment of furan in various food products. The optimised fibre exposure temperatures, time and amount of sample of liquid, semi solid and paste state foods were 5 g (ml), 50 °C, and 20 min, respectively. The level of furan in canned meat (32.16 ng/g) was the highest among the samples studied. The furan levels in canned fish, canned vegetable, nutritional/diet drinks, canned soups and jarred sauces were 29.40, 22.86, 7.28, 18.54 and 21.52 ng/g, respectively. Furan concentrations in baby food products were between 3.43 and 97.21 ng/g. Exposure estimates (14.59 ng/kg bw/day) of baby foods was the highest among all the tested food samples. However, the exposure estimate of baby foods was lower than that prescribed by the US FDA.     

Reliable estimation of dietary exposure to furan from coffee: An automatic vending machine as a case study

Worldwide Food Safety Agencies have classified furan as carcinogenic and cytotoxic due to its effects in animal studies, and it has been associated with harmful effects to human health. It has been pointed out that coffee consumption is the major contributor to dietary furan exposure for adults. However, furan is highly volatile and its losses due to volatilization in the cup during the time expend to consume the coffee brew should be taken into account for a realistic estimation of the levels of furan exposure for humans. The aim of this study was to estimate the furan exposure to humans considering the time for consumption after preparation of the fresh beverage. Furan was determined in coffee brews acquired from automatic coffee vending machines placed in areas with high density of population. Furan levels in coffee beverages ranged from 11 to 262 ng/mL (mean = 171 ± 59.8). Furthermore, five different scenarios were settled immediately after the acquisition of coffee brews from the coffee vending machines in order to assess a realistic estimation of furan exposure. Furan content in coffee decreased from 170 up to 4 ng/mL after simulating the behavior of coffee consumption (~ 74% after standing at room temperature for 5 min, ~ 64% after stirring for 30 s and standing at room temperature up to 5 min, ~ 94% after stirring for 5 min, ~ 97% after 8 h in a sealed thermo and ~ 37% after being cooled one week at a fridge). These results suggest that it is mandatory to establish very precisely the furan levels in the final ready-to-drink beverage in order to obtain reliable estimations of the daily intake from coffee and to define potential strategies for mitigation. Furan intake from coffee ranged from 0.02 to 0.43 μg/kg b.w./day, resulting in a mean exposure of 0.31 μg/kg b.w./day.     

Survey of furan in heat processed foods by headspace gas chromatography/mass spectrometry and estimated adult exposure

Furan is a suspected human carcinogen that is formed in some processed foods at low ng per g levels. Recent improvements in analytical methodology and scientific instrumentation have made it possible to accurately measure the amount of furan in a wide variety of foods. Results from analysis of more than 300 processed foods are presented. Furan was found at levels ranging from non-detectable (LOD, 0.2–0.9 ng g^?1) to over 100 ng g^?1. Exposure estimates for several adult food types were calculated, with brewed coffee being the major source of furan in the adult diet (0.15 µg kg^?1 body weight day^?1). Estimates of mean exposure to furan for different subpopulations were calculated. For consumers 2 years and older, the intake is estimated to be about 0.2 µg kg^?1 body weight day^?1.     

Are Chileans exposed to dietary furan?

Chilean consumer preferences include foods that may contain considerable amounts of furan, a potential human carcinogen. However, there is no information regarding dietary exposure to furan in Chile. Thus, the objective of this work was to determine the Chilean exposure to dietary furan. To accomplish this objective, the furan concentration of 14 types of commercial foods processed at high temperature were analysed based on a modified headspace-GC/MS (HS-GC/MS) method in which the limits of detection for different food matrices ranged from 0.01 to 0.6 ng g^?1. In addition, a risk assessment was made with exposure estimates based on dietary data from national studies on different age groups (9-month-old babies, school children, adults and elderly people). Of the food items surveyed “American”-type coffee (espresso coffee plus hot water) obtained from automatic coffee machine (936 ng g^?1) and low moisture starchy products like crisps and “soda”-type crackers showed the highest furan concentrations (259 and 91 ng g^?1, respectively). Furthermore, furan was also found in samples of breakfast cereals (approximately 20 ng g^?1), jarred fruit baby foods (8.5 ng g^?1) and orange juice (7.0 ng g^?1). School children (aged 9–13 years) represented the highest intake of furan (about 500 ng kg^?1_bw day^?1), with margins of exposure of 2479 and 2411, respectively, which points to a possible public health risk.     

咖啡中有关呋喃含量的研究进展

呋喃因其具有细胞毒性和致癌性,且在食品的热加工中极易产生而受到全世界的广泛关注,国际上的权威食品机构均出台了一系列关于呋喃的研究计划。咖啡是很常见的饮料,在咖啡豆烘焙过程中可产生很高含量的呋喃。本文将从呋喃的形成、咖啡制备过程对呋喃含量的影响因素和不同种类咖啡中呋喃含量的检测手段和研究进展进行综合论述,为今后对咖啡中的呋喃的研究提供资料参考。     

Dietary exposure to furan of the Austrian population

ABSTRACT

In the period from 2007 to 2017 furan levels of foods were analysed by the Austrian Agency for Health and Food Safety. Based on these analytical data and the Austrian consumption data the dietary exposure of children and adults to furan was estimated by using a deterministic approach. For the adult population the mean and 95^th percentile dietary exposures to furan were estimated at 0.31 µg/kg bodyweight per day and at 0.72 µg/kg bodyweight per day, respectively. The mean dietary exposure of children was estimated at 0.18 µg/kg bodyweight per day and is thus only about half as high as for Austrian adults. At the 95^th percentile the dietary exposure of children was estimated at 0.49 µg/kg bodyweight per day. The main contributor to the total dietary exposure for adults is coffee followed by convenience products and for children the main contributors are grain products as well as convenience products, bread and snacks. Based on the BMDL₁₀ of 0.064 mg/kg bodyweight per day for the development of cholangiofibrosis, the MOE-calculation revealed that the current levels of dietary exposure to furan are of concern for Austrian adult high consumers. The MOE-calculation, based on the BMDL₁₀ of 1.31 mg/kg bodyweight per day for the development of hepatocellular adenomas, indicated a health concern for Austrian children and adults.     

Assessment of dietary exposure of young Chinese children to aluminium residues

The aim of this study was to assess the Al dietary exposure of young Chinese children aged 0–3 years via formulae, complementary foods and wheat-based foods. Al residue data were obtained from the national food contamination monitoring programme from 2013 to 2016, encompassing 13,833 samples of 12 food items with a detection rate of 76.0%. Food consumption data were gathered from the China National Food Consumption Survey conducted in 2015, comprising 20,172 children aged 0–3 years old. The mean dietary exposure to Al for the general population of young Chinese children was estimated at 0.76 mg/kg bw/week, which does not exceed the PTWI. The 97.5th percentile intakes of Al reached 3.42 mg/kg bw/week, more than 1.7 times the PTWI. Wheat-based foods contributed 80.5% of the Al intake for the general population of young Chinese children, while formulae and complementary foods accounted for 19.5% of the total intake. The dietary intake of Al from formulae and complementary foods accounted for 6.0% and 1.6% of PTWI, respectively. These findings suggested that dietary exposure to Al among the general population of young Chinese children was lower than the PTWI and that there are no health concerns related to this level of Al intake. However, more attention should be placed on the health risks associated with Al exposure from wheat-based foods for young consumers with high food consumption in China (97.5th percentile)     

Estimate of dietary exposure to sulphites using Brazilian students as a sample population.

In Brazil, there is neither a register of the use of sulphites by the food industry nor is research being undertaken on their dietary exposure to the population. The objective of the work reported here was to estimate the dietary exposure to sulphites in two different groups of high school students, a fee-paying school group and a state school group. The data were collected through a 24-hour dietary recall, which provided estimates of sulphited foods and beverages in the diet. The Maximum Permitted Level (MPL), established by the Brazilian legislation for each of the sulphited food and beverages, was used to measure the dietary exposure to this additive. On this basis none of the students could have exceeded the Acceptable Daily Intake (ADI) of 0.70 mg SO2/kg bw/day, with a average dietary exposure of 0.07 mg SO2/kg bw/day (p<0.001), with no significant statistical difference (p=0.643) between fee-paying and state school students. Highly exposed consumers (dietary exposure to more than 50% of the ADI, or either, 0.35 mg SO2/kg bw/day, to the maximum of 0.52 mg SO2/kg bw/dia) represented 4.5% of the researched samples and reached these levels of intake due to a consumption beyond 500 ml/day of industrialized packaged fruit juices, and, in the fee-paying school, for associating its consumption with alcoholic beverages like beer and wine.     

Dietary exposure to acrylamide in a group of Japanese adults based on 24-hour duplicate diet samples

Acrylamide is a probable human carcinogen and known human neurotoxin that can be generated in food through heating. Using a mathematical modelling approach, our previous study estimated long-term average dietary exposure to acrylamide in the Japanese people; however, the validity of these estimates remained unknown. Here, we aimed to obtain a more accurate estimate of acrylamide exposure that would reflect the usual practice of heat processing and consumption of foods in the population. We collected duplicate diet samples and dietary records during 24 h from a group of Japanese adults. A total of 110 duplicate diet samples were analysed for acrylamide by LC-MS/MS. Data from individual dietary records were used to examine the association between dietary acrylamide exposure and consumption of selected food groups (e.g., coffee, tea, confectioneries, and vegetables prepared at high temperature [deep-frying, stir-frying, sautéing, and baking]). Of the 110 homogenised diet samples, 108 contained detectable levels of acrylamide. Dietary exposure to acrylamide ranged from 8 to 1582 ng/kg body weight (bw)/day, with the mean value of 215 ng/kg-bw/day and median value of 143 ng/kg-bw/day. This mean value was higher than the value we previously estimated for Japanese adults using a mathematical approach. Multiple linear regression analysis showed log dietary acrylamide exposure was significantly associated with consumption of coffee and vegetables prepared at high temperature during 24-hr of sampling (adj. R² = 0.250, p < 0.001). We revealed significant difference in dietary acrylamide exposure between participants who had coffee and vegetables prepared at high temperature (median, 169 ng/kg-bw/day; range, 35–1224 ng/kg-bw/day, n = 42) and those who had none of them (median, 75 ng/kg-bw/day; range, 8–311 ng/kg-bw/day, n = 15) (Steel-Dwass test, p < 0.05).     

Some factors affecting the formation of furan in heated foods

Levels of furan in various foods were measured before and after heating under heating and laboratory conditions. The effect of contact with can coatings, sealing gaskets and the epoxidized oils used in gasket manufacture on furan formation was studied. The objective was to identify factors affecting furan formation. Furan present in heat-processed food samples persisted during cooking. Furan was shown to form in foods on heating, although it did not accumulate to a significant degree on heating in an open vessel. There were no interactions between foods and cans, can coatings or gaskets that had a significant influence on furan formation. Furan accumulated particularly in heat-processed canned and jarred foods because they are sealed containers that receive a considerable thermal load. Heating epoxidized oils used in sealing gaskets formed furan. At the levels used in gaskets, however, epoxidized oils should not affect the formation of furan in foods.     

A Preliminary Investigation of Naturally Occurring Aluminum in Grains,Vegetables, and Fruits from Some Areas of China and Dietary Intake Assessment

An investigation of the naturally occurring aluminum contents in grains, fruits and vegetables locally planted in some areas of China was conducted, and the aluminum dietary intake from the investigated food was estimated. A total of 2,469 samples were collected during 2013 to 2014 and tested for aluminum content using ICP‐MS method. The results showed that although 77.6% of the samples contained aluminum less than 5 mg/kg, significant variations of aluminum contents were observed in different food groups. Generally, the aluminum contents were found to be relatively high in dried grains and fresh vegetables, and low in fresh fruits. The mean value of aluminum contents in grains was 6.3 mg/kg, with wheat being the highest, followed by soybean and corn. The fresh vegetables had an average aluminum content of 4.7 mg/kg, with leafy vegetables being the highest, followed by bulb and stem vegetables. Most varieties of fresh fruits were low in aluminum, with the mean of 1.3 mg/kg. Based on the food consumption data from the China National Nutrient and Health Survey, the average weekly dietary intake of naturally occurring aluminum from the investigated foods was estimated to be 0.62 mg/kg bw for the general population and 0.55 to 1.00 mg/kg bw for different age groups. Grains and vegetables were the main contributors to the overall intake. Evaluated against the provisional tolerable weekly intake (PTWI) of 2 mg/kg bw, the dietary naturally occurring aluminum intake from the investigated foods was considered to be no safety concern.     

饼干中苯甲酸及其钠盐含量分析及其膳食暴露评估

对市场中210个饼干样品进行苯甲酸及其钠盐含量用HPLC方法进行测定,并对检测数据采用膳食暴露评估方法,评估城市居民的膳食风险。结果显示,婴儿(6～12个月)膳食暴露量为12.25～31.62μg/kg bw·d,其97.5/99百分位值的膳食暴露量为73.99～195.62μg/kg bw·d,建议婴儿(6～12个月)少量食用或食用不含苯甲酸的婴儿饼干。对于1～3岁的幼儿其膳食暴露量为10.25～13.25μg/kg bw·d,在97.5/99百分位值的膳食暴露量为105.24～139.10μg/kg bw·d,食用此类食品的风险是可以接受的。对于3岁以上人群食用此类食品的风险比1～3岁幼儿更小,风险程度更低。另外,饼干中威化和酥性类饼干中苯甲酸的残留水平相对于其他类饼干含量略高,而发酵和韧性类的饼干中苯甲酸的含量相稍低;同时显示江苏产的产品质量相对较好。     

Acrylamide levels and dietary exposure from foods in the United States,an update based on 2011-2015 data

ABSTRACT

Acrylamide is a contaminant that can form in certain plant-based foods during high-temperature cooking. From 2011–2015, the Food and Drug Administration conducted extensive sampling and analyses of acrylamide in foods, as a follow-up to surveys from 2002–2006. We compared acrylamide occurrence data and exposure estimates based on 2011–2015 data with data and exposure estimates from 2002–2006. Acrylamide levels in selected food categories generally did not decrease significantly in 2011–2015 compared with 2002–2006. However, significant decreases in acrylamide concentrations were observed for potato chips and crackers, which may be related to the availability and use of mitigation techniques for reducing acrylamide in foods. Mean dietary intake for those 2 years and older based on 2011–2015 data was 0.36 µg/kg bw/day, comparable to the 0.44 µg/kg bw/day reported by FDA in 2006. French fries and potato products, breakfast cereal, cookies, potato chips, and crackers continue to be the greatest contributors to dietary intake of acrylamide. Infant snack foods were identified as an important contributor to acrylamide intake relative to infant jarred foods. The continued presence of acrylamide in food suggests that manufacturers and governments should continue to pursue efforts to reduce acrylamide in foods that are important contributors to acrylamide intake.