The JFFMA assessment of flavoring substances structurally related to menthol and uniquely used in Japan

Using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), we performed safety evaluations on four flavoring substances structurally related to menthol (l-menthyl 2-methylbutyrate, dl-menthyl octanoate, dl-menthyl palmitate, and dl-menthyl stearate) uniquely used in Japan. While no genotoxicity study data were available in the literature, all four substances had no chemical structural alerts predictive of genotoxicity. Moreover, they all four are esters consisting of menthol and simple carboxylic acids that were assumed to be immediately hydrolyzed after ingestion and metabolized into innocuous substances for excretion. As menthol and carboxylic acids have no known genotoxicity, it was judged that the JECFA procedure could be applied to these four substances. According to Cramer’s classification, these substances were categorized as class I based on their chemical structures. The estimated daily intakes for all four substances were within the range of 1.54–4.71 μg/person/day and 60–1250 μg/person/day, using the methods of Maximized Survey-Derived Intake and Single Portion Exposure Technique, respectively, based on the annual usage data of 2001, 2005, and 2010 in Japan. As the daily intakes of these substances were below the threshold of concern applied to class I substances viz., 1800 μg/person/day, it was concluded that all four substances raise no safety concerns when used for flavoring foods under the currently estimated intake levels.     

Chronic dietary risk characterization for pesticide residues: A ranking and scoring method integrating agricultural uses and food contamination data

A method has been developed to identify pesticide residues and foodstuffs for inclusion in national monitoring programs with different priority levels. It combines two chronic dietary intake indicators: ATMDI based on maximum residue levels and agricultural uses, and EDI on food contamination data. The mean and 95th percentile of exposure were calculated for 490 substances using individual and national consumption data. The results show that mean ATMDI exceeds the acceptable daily intake (ADI) for 10% of the pesticides, and the mean upper-bound EDI is above the ADI for 1.8% of substances. A seven-level risk scale is presented for substances already analyzed in food in France and substances not currently sought. Of 336 substances analyzed, 70 pesticides of concern (levels 2-5) should be particularly monitored, 22 of which are priority pesticides (levels 4 and 5). Of 154 substances not sought, 36 pesticides of concern (levels 2-4) should be included in monitoring programs, including 8 priority pesticides (level 4). In order to refine exposure assessment, analytical improvements and developments are needed to lower the analytical limits for priority pesticide/commodity combinations. Developed nationally, this method could be applied at different geographic scales.     

Risk characterization for mercury, dichlorodiphenyltrichloroethane and polychlorinated biphenyls associated with fish consumption in Serbia

The aim of this work was to assess the risk due to mercury (Hg), dichlorodiphenyltrichloroethane (DDT) and non-dioxin-like polychlorinated biphenyls (ndl PCBs) intake via fish consumption in Serbia. We have developed 24 scenarios using four concentration levels (mean, maximum, 50th and 95th percentile) of contaminants, determined in 521 samples of fish products available on Serbian market; two consumption levels (Food and Agriculture Organization/World Health Organization data and recommendation of American Heart Association); and three body weights (5th, 50th and 95th percentile). All the values concerning the intake of DDT are below the corresponding health based guidance value. Calculated weekly intake of Hg using maximal concentration, intake of 340 g/week and 5th percentile of body weight exceeded the provisional tolerable weekly intake (PTWI). When maximal and 95th percentile concentration of ndl PCBs was used, weekly intakes exceeded a “guidance value” with one exception i.e., when 95th percentile of concentration along with 95th percentile of body weight were used. Concerning Hg and ndl PCBs, when extreme concentrations were used, HIs exceeded the value of 1, indicating that fish and fishery products may pose a threat to consumer’s health.     

Cumulative risk assessment of pesticide residues in food

There is increasing need to address the potential risks of combined exposures to multiple residues from pesticides in the diet. The available evidence suggests that the main concern is from dose addition of those compounds that act by the same mode of action. The possibility of synergy needs to be addressed on a case-by-case basis, where there is a biologically plausible hypothesis that it may occur at the levels of residues occurring in the diet. Cumulative risk assessment is a resource-intense activity and hence a tiered approach to both toxicological evaluation and intake estimation is recommended, and the European Food Safety Authority (EFSA) has recently published such a proposal. Where assessments have already been undertaken by some other authority, full advantage should be taken of these, subject of course to considerations of quality and relevance. Inclusion of compounds in a cumulative assessment group (CAG) should be based on defined criteria, which allow for refinement in a tiered approach. These criteria should include chemical structure, mechanism of pesticidal action, target organ and toxic mode of action. A number of methods are available for cumulating toxicity. These are all inter-related, but some are mathematically more complex than others. The most useful methods, in increasing levels of complexity and refinement, are the hazard index, the reference point index, the Relative Potency Factor method and physiologically based toxicokinetic modelling, although this last method would only be considered should a highly refined assessment be necessary. Four possible exposure scenarios are of relevance for cumulative risk assessment, acute and chronic exposure in the context of maximum residue level (MRL)-setting, and in relation to exposures from the actual use patterns, respectively. Each can be addressed either deterministically or probabilistically. Strategies for dealing with residues below the limit of detection, limit of quantification or limit of reporting need to be agreed. A number of probabilistic models are available, but some of there are geographically constrained due to the underlying datasets used in their construction. Guidance on probabilistic modelling needs to be finalised. Cumulative risk assessments have been performed in a number of countries, on organophosphate insecticides alone (USA) or together with carbamates (UK, DK, NL), triazines, chloroacetanilides, carbamates alone (USA), and all pesticides (DE). All identifiable assumptions and uncertainties should be tabulated and evaluated, at least qualitatively. Those likely to have a major impact on the outcome of the assessment should be examined quantitatively. In cumulative risk assessment, it is necessary, as in other risk assessments, for risk managers to consider what level of risk would be considered "acceptable", for example what percentile of the population should be below the reference value. Criteria for prioritising CAGs for cumulative risk assessment include frequency of detection in monitoring programmes, high usage, high exposure relative to the reference value, large number of compounds (e.g. five or more) in a group.     

First European conference on aspartame: putting safety and benefits into perspective. Synopsis of presentations and conclusions.

A Conference was held in Paris in 2006 to review the safety and benefits arising from the replacement of sucrose with the intense sweetener aspartame. The intakes of aspartame are only about 10% of the acceptable daily intake, even by high consumers, so that the safety margin is about 3 orders of magnitude. The safety of aspartame was confirmed in the EFSA Opinion of a recent controversial rodent cancer bioassay. There is increasing evidence that even modest reductions in the intake of calories can reduce the risk factors associated with a number of diseases, such as diabetes and cardiovascular disease. A key issue addressed at the conference was whether the replacement of sucrose with aspartame could result in a prolonged decrease in calorie intake that was of similar magnitude to that necessary to produce a health benefit. A recent meta-analysis of published data showed that an adequate, prolonged weight reduction could be achieved with aspartame. It was recognised that risk assessment alone gave an unbalanced impression to regulators and consumers, and that in the future quantitative risk-benefit analyses should be able to provide more comprehensive advice.     

Estimation of ochratoxin A in some Turkish populations: An analysis in urine as a simple,sensitive and reliable biomarker

In this study, ochratoxin A (OTA) occurrence and level in human urine samples, collected from four different regions of Turkey was analyzed by NaHCO₃ dilution, immunoaffinity column clean-up and high-performance liquid chromatography with fluorescent detection. For the repeatability of the method, RSD (%) values were found between 3.83 and 8.86, for the accuracy, the recovery values were found between 85.7% and 110.5% and limit of detection and limit of quantification of the method were measured as 0.006 and 0.018 ng mL⁻¹ respectively. For the analysis, first morning urine samples were collected and the results were adjusted with creatinine levels. From the total collected samples of 233 larger amounts of 83% was contaminated with OTA. Among the calculated to be OTA levels, positive sample rate, average OTA amount and the highest contamination was found in Ankara. (Positive sample rate; 90.1%, average OTA concentration; 14.34 ng g⁻¹ creatinine and highest OTA value; 75.60 ng g⁻¹ creatinine). In order to define the exposure profile of OTA in human a questionnaire was conducted among the voluntaries as well. But related to the gender, age, dietary habits, coffee consumption, smoking and alcohol habits of the volunteers, no correlation was found with the OTA exposure.     

In vitro enrofloxacin binding in human fecal slurries

Most antibiotic inactivation studies have been conducted through in vitro incubations of human use aminoglycosides, beta-lactams, and fluoroquinolones, usually at fecal concentrations expected with therapeutic dose regimens in humans and animals. Less is known about the inactivation of these molecules when ingested at concentrations consistent with residue levels present in animal-derived foods from antibiotic treated animals. In this investigation, we used the fluoroquinolone, enrofloxacin which is specifically marketed for veterinary medicine as test compound. Fecal suspensions at 10%, 25%, and 50% (w/v) were subjected to physicochemical and molecular characterization and used in the drug binding studies. The fecal binding of enrofloxacin added at concentrations of 0.06, 0.1, 1, 5, 15, 50, and 150 mg/L was determined in various fecal slurry suspensions using analytical chemistry and microbiological assay methods. There was consistent correlation between both assay methods. By the analytical chemistry assay, the 10%, 25% and 50% diluted autoclaved fecal samples dosed with enrofloxacin showed binding of 50±4.6%, 54±6.5% and 56±6.8% of the enrofloxacin, respectively. Binding of enrofloxacin to fecal contents occurred rapidly within 10 min and remained constant over the incubation period. Denaturing gradient gel electrophoreses and pyrosequencing analysis showed varied profiles of the bacterial composition of the human intestinal microbiota for fecal samples from different individuals. This study provided information on methodological questions that have concerned regulatory authorities on in vitro testing to determine if concentrations of veterinary antimicrobial agent residues entering the human colon remain microbiologically active.     

Assessment of possible allergenicity of hypothetical ORFs in common food crops using current bioinformatic guidelines and its implications for the safety assessment of GM crops

Before a genetically modified (GM) crop can be commercialized it must pass through a rigorous regulatory process to verify that it is safe for human and animal consumption, and to the environment. One particular area of focus is the potential introduction of a known or cross-reactive allergen not previously present within the crop. The assessment of possible allergenicity uses the guidelines outlined by the Food and Agriculture Organization (FAO) and World Health Organization’s (WHO) Codex Alimentarius Commission (Codex) to evaluate all newly expressed proteins. Some regulatory authorities have broadened the scope of the assessment to include all DNA reading frames between stop codons across the insert and spanning the insert/genomic DNA junctions. To investigate the utility of this bioinformatic assessment, all naturally occurring stop-to-stop frames in the non-transgenic genomes of maize, rice, and soybean, as well as the human genome, were compared against the AllergenOnline (www.allergenonline.org) database using the Codex criteria. We discovered thousands of frames that exceeded the Codex defined threshold for potential cross-reactivity suggesting that evaluating hypothetical ORFs (stop-to-stop frames) has questionable value for making decisions on the safety of GM crops.     

Safety assessment of diacylglycerol oil as an edible oil: A review of the published literature

Diacylglycerol oil is an edible oil with taste and usability characteristics comparable to naturally occurring oils. The objective of this review is to examine literature on diacylglycerol oil to assess its safety-in-use. Feeding rats with unheated or heated diacylglycerol oil at levels up to 5.5% in diet for 90 days did not cause any toxic effects. In chronic studies, dietary administration of diacylglycerol oil (up to 5.3%) to rats for 2 years or at 9.5% to Beagle dogs for 1 year had no adverse effects. Genotoxicity studies of unheated and heated diacylglycerol oil did not reveal any genotoxic effects. Carcinogenicity studies in rodents demonstrate that diacylglycerol oil is non-carcinogenic. In a two-generation reproductive and developmental toxicity study, gavage administration of diacylglycerol oil at dose levels of 5.0 ml/kg body weight/day did not reveal any adverse effects. In several human clinical investigations, administration of diacylglycerol oil at levels up to 0.5 g/kg body weight/day for up to 1 year did not cause adverse effects. Collectively, there is sufficient qualitative and quantitative scientific evidence available from animal and human studies suggesting that intake of diacylglycerol oil is safe for human consumption when used in a manner similar to other edible oils.     

Locust bean gum safety in neonates and young infants: An integrated review of the toxicological database and clinical evidence

Locust bean gum (LBG) is a galactomannan polysaccharide used as thickener in infant formulas with the therapeutic aim to treat uncomplicated gastroesophageal reflux (GER). Since its use in young infants below 12 weeks of age is not explicitly covered by the current scientific concept of the derivation of health based guidance values, the present integrated safety review aimed to compile all the relevant preclinical toxicological studies and to combine them with substantial evidence gathered from the clinical paediatric use as part of the weight of evidence supporting the safety in young infants below 12 weeks of age. LBG was demonstrated to have very low toxicity in preclinical studies mainly resulting from its indigestible nature leading to negligible systemic bioavailability and only possibly influencing tolerance. A standard therapeutic level of 0.5 g/100 mL in thickened infant formula is shown to confer a sufficiently protective Margin of Safety. LBG was not associated with any adverse toxic or nutritional effects in healthy term infants, while there are limited case-reports of possible adverse effects in preterms receiving the thickener inappropriately. Altogether, it can be concluded that LBG is safe for its intended therapeutic use in term-born infants to treat uncomplicated regurgitation from birth onwards.     

Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth

Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.     

Incidence of aflatoxins in Iran pistachio nuts.

Aflatoxins (AF) are highly toxic and carcinogenic secondary fungal metabolites and have been detected in various food commodities including pistachio nuts. Pistachio nuts were produced in Iran during March 2002-February 2003 analyzed for aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and aflatoxin G2 (AFG2) using immunoaffinity column and quantitated by HPLC and/or TLC-scanner. In this regard, 3356 pistachio nut samples were collected. After dividing samples to sub-samples, 10,068 AF analyses were done. Among 10,068 samples analyzed, AFB1 was detected in 3699 samples (36.7% of the total) with the mean and median of 5.9 (+/-41.7) ng/g and 0.1 ng/g, respectively. Total AF (AFT) was detected in 2852 samples (28.3% of the total) with the mean and median of 7.3 (+/-53.2)ng/g and 0.4 ng/g, respectively. AFB1 level in 1191 samples (11.8%) was above the maximum tolerated level (MTL) of AFB1 in pistachio nut in Iran (5 ng/g). Regarding AFT, the mean contamination level (7.3 ng/g) was lower than MTL of AFT in pistachio nut in Iran as well as lower than the proposed draft maximum level of Codex Committee on Food Additives and Contaminants for AFT (15 ng/g), and only 7.5% of samples had levels above the MTL.     

Individual methylmercury intake estimates from local seafood of the Mediterranean Sea,in Italy

A Seafood Frequency Questionnaire (SFQ) broken down in more than 42 items with 8-week coverage was interview-administered to 278 adults aged 19–82 years (167 women, 98 in the reproductive age 19–45 years, and 111 men), resident on the Italian Mediterranean shore and frequent buyer at local fish markets. Methylmercury (MeHg) intake on individual basis was estimated for a selected occurrence equal to the median value + Median Absolute Deviation (MAD) in each seafood species reported (conservative scenario). MeHg occurrence was derived from an extensive seafood database referred to years 2009–2011. Accounting for an average body weight of 62.2 kg, 24.6% of women resulted overexposed with respect to the European Food Safety Authority (EFSA) Tolerable Weekly Intake (TWI) for MeHg of 1.3 μg/kg bw, with a mean of 0.92 μg/kg bw. In the vulnerable group aged 19–45 years, 29.6% exceeded the TWI. Rather than the amount of seafood consumed, the seafood choice appears to be the main determinant of the MeHg intake. Risk awareness was reported in the 49% of SFQs. Uncertainties related to such estimates from questionnaires are discussed, in order to give adequate health recommendations without compromising seafood consumption in the Mediterranean region.     

Safety assessment of personal care products/cosmetics and their ingredients

We attempt to review the safety assessment of personal care products (PCP) and ingredients that are representative and pose complex safety issues. PCP are generally applied to human skin and mainly produce local exposure, although skin penetration or use in the oral cavity, on the face, lips, eyes and mucosa may also produce human systemic exposure. In the EU, US and Japan, the safety of PCP is regulated under cosmetic and/or drug regulations. Oxidative hair dyes contain arylamines, the most chemically reactive ingredients of PCP. Although arylamines have an allergic potential, taking into account the high number of consumers exposed, the incidence and prevalence of hair dye allergy appears to be low and stable. A recent (2001) epidemiology study suggested an association of oxidative hair dye use and increased bladder cancer risk in consumers, although this was not confirmed by subsequent or previous epidemiologic investigations. The results of genetic toxicity, carcinogenicity and reproductive toxicity studies suggest that modern hair dyes and their ingredients pose no genotoxic, carcinogenic or reproductive risk. Recent reports suggest that arylamines contained in oxidative hair dyes are N-acetylated in human or mammalian skin resulting in systemic exposure to traces of detoxified, i.e. non-genotoxic, metabolites, whereas human hepatocytes were unable to transform hair dye arylamines to potentially carcinogenic metabolites. An expert panel of the International Agency on Research of Cancer (IARC) concluded that there is no evidence for a causal association of hair dye exposure with an elevated cancer risk in consumers. Ultraviolet filters have important benefits by protecting the consumer against adverse effects of UV radiation; these substances undergo a stringent safety evaluation under current international regulations prior to their marketing. Concerns were also raised about the safety of solid nanoparticles in PCP, mainly TiO₂ and ZnO in sunscreens. However, current evidence suggests that these particles are non-toxic, do not penetrate into or through normal or compromised human skin and, therefore, pose no risk to human health. The increasing use of natural plant ingredients in personal care products raised new safety issues that require novel approaches to their safety evaluation similar to those of plant-derived food ingredients. For example, the Threshold of Toxicological Concern (TTC) is a promising tool to assess the safety of substances present at trace levels as well as minor ingredients of plant-derived substances. The potential human systemic exposure to PCP ingredients is increasingly estimated on the basis of in vitro skin penetration data. However, new evidence suggests that the in vitro test may overestimate human systemic exposure to PCP ingredients due to the absence of metabolism in cadaver skin or misclassification of skin residues that, in vivo, remain in the stratum corneum or hair follicle openings, i.e. outside the living skin. Overall, today's safety assessment of PCP and their ingredients is not only based on science, but also on their respective regulatory status as well as other issues, such as the ethics of animal testing. Nevertheless, the record shows that today's PCP are safe and offer multiple benefits to quality of life and health of the consumer. In the interest of all stakeholders, consumers, regulatory bodies and producers, there is an urgent need for an international harmonization on the status and safety requirements of these products and their ingredients.     

The benchmark dose approach in food risk assessment: Is it applicable and worthwhile?

The benchmark dose (BMD) approach is being increasingly used in the area of food risk assessment because it offers several advantages compared to the conventional no-observed-adverse-effect-level approach. The aim of this work was to check the applicability of the BMD approach on toxicity data available from pesticides, mycotoxins and natural toxins.     

Application of the threshold of toxicological concern approach for the safety evaluation of calendula flower (Calendula officinalis) petals and extracts used in cosmetic and personal care products

Calendula flower (Calendula officinalis) (CF) has been used in herbal medicine because of its anti-inflammatory activity. CF and C. officinalis extracts (CFE) are used as skin conditioning agents in cosmetics. Although data on dermal irritation and sensitization of CF and CFE’s are available, the risk of subchronic systemic toxicity following dermal application has not been evaluated. The threshold of toxicological concern (TTC) is a pragmatic, risk assessment based approach that has gained regulatory acceptance for food and has been recently adapted to address cosmetic ingredient safety. The purpose of this paper is to determine if the safe use of CF and CFE can be established based upon the TTC class for each of its known constituents. For each constituent, the concentration in the plant, the molecular weight, and the estimated skin penetration potential were used to calculate a maximal daily systemic exposure which was then compared to its corresponding TTC class value. Since the composition of plant extracts are variable, back calculation was used to determine the maximum acceptable concentration of a given constituent in an extract of CF. This paper demonstrates the utility and practical application of the TTC concept when used as a tool in the safety evaluation of botanical extracts.     

On the occurrence of aflatoxin M1 in milk and dairy products

Aflatoxins are toxic fungal metabolites found in foods and feeds. When ruminants eat AFB₁-feedstuffs, they metabolise the toxin and excrete AFM₁ in milk. To control AFM₁ in foods it is necessary to reduce AFB₁ contamination of feeds for dairy cattle by preventing fungal growth and AFB₁ formation in agricultural commodities intended for animal use. Corn and corn-based products are one of the most contaminated feedstuffs; therefore risk factor analysis of AFB₁ contamination in corn is necessary to evaluate risk of AFM₁ contamination in milk and milk products. During the corn silage production, the aflatoxins production is mostly influenced by: harvest time; fertilization; irrigation; pest control; silage moisture; and storage practices. Due to the lower moisture at harvest and to the conservation methods, the corn grain is mostly exposed to the contamination by Aspergillus species. Therefore, it is necessary to reduce the probability of this contaminant through choice of: hybrids; seeding time and density; suitable ploughing and fertirrigation; and chemical or biological control. Grains harvested with the lowest possible moisture and conservation moisture close to or less than 14% are necessary to reduce contamination risks, as is maintaining mass to homogeneous moisture. Kernel mechanical damage, grain cleaning practices and conservation temperature are also factors which need to be carefully controlled.     

Safety assessment of myristic acid as a food ingredient.

Myristic acid is used in the food industry as a flavor ingredient. It is found widely distributed in fats throughout the plant and animal kingdom, including common human foodstuffs, such as nutmeg. Myristic acid (a 14-carbon, straight-chain saturated fatty acid) has been shown to have a low order of acute oral toxicity in rodents. It may be irritating in pure form to skin and eyes under exaggerated exposure conditions, but is not known or predicted to induce sensitization responses. Myristic acid did not induce a mutagenic response in either bacterial or mammalian systems in vitro. Relevant subchronic toxicity data are available on closely related fatty acid analogs. In particular, a NOEL of >6000mg/kg was reported for lauric acid (a 12-carbon, straight-chain saturated fatty acid) following dietary exposure to male rats for 18 weeks and a NOEL of >5000mg/kg was reported for palmitic acid (a 16-carbon, straight-chain saturated fatty acid) following dietary exposure to rats for 150 days. The data and information that are available indicate that at the current level of intake, food flavoring use of myristic acid does not pose a health risk to humans.     

Metabolism of the masked mycotoxin deoxynivalenol-3-glucoside in rats

Deoxynivalenol-3-β-d-glucoside (D3G), a plant metabolite of the Fusarium mycotoxin deoxynivalenol (DON), might be hydrolyzed in the digestive tract of mammals, thus contributing to the total dietary DON exposure of individuals. Yet, D3G has not been considered in regulatory limits set for DON for foodstuffs due to the lack of in vivo data. The aim of our study was to evaluate whether D3G is reactivated in vivo by investigation of its metabolism in rats. Six Sprague-Dawley rats received water, DON (2.0mg/kg body weight (b.w.)) and the equimolar amount of D3G (3.1mg/kg b.w.) by gavage on day 1, 8 and 15, respectively. Urine and feces were collected for 48h and analyzed for D3G, DON, deoxynivalenol-glucuronide (DON-GlcA) and de-epoxy deoxynivalenol (DOM-1) by a validated LC-tandem mass spectrometry (MS/MS) based biomarker method. After administration of D3G, only 3.7±0.7% of the given dose were found in urine in the form of analyzed analytes, compared to 14.9±5.0% after administration of DON, and only 0.3±0.1% were detected in the form of urinary D3G. The majority of administered D3G was recovered as DON and DOM-1 in feces. These results suggest that D3G is little bioavailable, hydrolyzed to DON during digestion, and partially converted to DOM-1 and DON-GlcA prior to excretion. Our data indicate that D3G is of considerably lower toxicological relevance than DON, at least in rats.