Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts

Honda, Hiroshi; Fujii, Kenkichi; Yamaguchi, Tohru; Ikeda, Naohiro; Nishiyama, Naohiro; Kasamatsu, Toshio

doi:10.1016/j.fct.2012.07.058

Cited by 34 publications

(18 citation statements)

References 24 publications

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“…Honda et al. () investigated levels of N‐(2,3‐dihydroxypropyl)valine adducts in blood of donors who consumed over a 4‐month period a DAG‐rich oil, previously reported to contain significantly higher levels of GE than regular cooking oils. While background adducts were measurable in all donors, no significant difference was observed between the DAG oil consumers and non‐consumers (Honda et al., ).…”

Section: Assessmentmentioning

confidence: 99%

“…Previous biomonitoring studies have shown that humans are continuously exposed to exogenous (and possibly also endogenous) sources of glycidol or glycidol-like compounds forming N-(2,3dihydroxypropyl)valine adducts in blood (Hindsø Landin et al, 1997). Honda et al (2012) investigated levels of N-(2,3-dihydroxypropyl)valine adducts in blood of donors who consumed over a 4-month period a DAG-rich oil, previously reported to contain significantly higher levels of GE than regular cooking oils. While background adducts were measurable in all donors, no significant difference was observed between the DAG oil consumers and non-consumers .…”

Section: Protein/dna Adductsmentioning

confidence: 99%

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Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Wallace¹,

Alexander²,

Barregård³

et al. 2016

EFS2

132

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EFSA was asked to deliver a scientific opinion on free and esterified 3-and 2-monochloropropane-1, 2-diol (MCPD) and glycidyl esters in food. Esters of 3-and 2-MCPD and glycidol are contaminants of processed vegetable oils; free MCPDs are formed in some processed foods. The Panel on Contaminants in the Food Chain (CONTAM Panel) evaluated 7,175 occurrence data. Esters of 3-and 2-MCPD and glycidyl esters were found at the highest levels in palm oil/fat, but most vegetable oil/fats contain substantial quantities. Mean middle bound (MB) dietary exposure values to total 3-MCPD, 2-MCPD and glycidol, respectively, across surveys and age groups in µg/kg body weight (bw) per day were 0.2-1.5, 0.1-0.7 and 0.1-0.9; high exposure (P95) values were 0.3-2.6, 0.2-1.2 and 0.2-2.1. Animal studies show extensive hydrolysis of esterified 3-MCPD and glycidol following oral administration; esterified and free forms were assumed to contribute equally to internal exposures. Nephrotoxicity was consistently observed in rats treated with 3-MCPD. Data on 2-MCPD toxicity were insufficient for dose-response assessments. Chronic treatment with glycidol increased the incidence of tumours in several tissues of rats and mice, likely via a genotoxic mode of action. The Panel selected a BMDL 10 value for 3-MCPD of 0.077 mg/kg bw per day for induction of renal tubular hyperplasia in rats and derived a tolerable daily intake (TDI) of 0.8 µg/kg bw per day. The mean exposure to 3-MCPD was above the TDI for 'Infants', 'Toddlers' and 'Other children'. For glycidol, the Panel selected a T25 value of 10.2 mg/kg bw per day for neoplastic effects in rats. The margins of exposure (MoEs) were 11,300-102,000 and 4,900-51,000 across surveys and age groups at mean and P95 exposures, respectively. An exposure scenario for infants receiving formula only resulted in MoEs of 5,500 (mean) and 2,100 (P95). MoEs of 25,000 or higher were considered of low health concern. Amendment: A few editorial amendments were carried out that do not materially affect the contents of the outcome of this scientific output: on pages 5 and 91 'chorine' has been replaced with 'chlorine'; on page 52 the word 'it' has been replaced by 'its' in the first paragraph after Figure 7; on page 54 in the Repeated dose section the reference to MCPD has been replaced with 3-MCPD; on page 54 the 429.5 mg/kg bw day dose has been replaced with 29.5 mg/kg bw day; on page 55 in the first paragraph of the Hematology section the reference 'mg/kg per day' has been replaced with 'mg/kg bw per day; on page 55 the year for the reference Marchesini et al. has been changed from 1989 to 1986; on page 59, in the first paragraph of the Developmental toxicity section the word 'days' has been cancelled; on page 65 the reference 'Onami et al., 2014a,b' has been replaced with 'Onami et al., 2014b'; on page 85 first paragraph, reference to the lowest T25 of 10 has been replaced to 10.2. To avoid confusion, the older version has been removed from the EFSA Journal, but is available on request, as is a version sho...

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Section: Assessmentmentioning

confidence: 99%

Section: Protein/dna Adductsmentioning

confidence: 99%

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Wallace¹,

Alexander²,

Barregård³

et al. 2016

EFS2

132

View full text Add to dashboard Cite

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“…The fit of the cumulative data from all participants is added for the sake of comparison (dashed line). Please note that the latter lines vary in height depending on the respective individual body weight and due to the use for cooking at home, compared to subjects not exposed to this oil (Honda et al 2012). However, the interpretability of the study is limited due to the missing control of the exposure to fatty acid esters of glycidol in both groups.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, formation of glycidol during domestic food preparation may play a role, as well as inhalational exposure, e.g., from passive smoking. Theoretically, an endogenous formation may also contribute to the internal exposure (Honda et al 2012(Honda et al , 2014.…”

Section: Estimate Of the Glycidol Exposure From The Adduct Levelmentioning

confidence: 99%

“…Research initiated following the discovery of glycidyl esters in food has already demonstrated the applicability of 2,3-diHOPr-Val as a marker of internal exposure in rodents treated with high doses of orally administered glycidol (Aasa et al 2017a;Appel et al 2013;Honda et al 2014). Surprisingly, the levels of 2,3-diHOPr-Val in blood samples from an observational study with participants exposed to a glycidyl ester-rich vegetable oil did not differ from those not exposed to this oil (Honda et al 2012). However, the interpretability of the study is limited due to the lack of data on the actual glycidol exposure of the participants.…”

Section: Introductionmentioning

confidence: 99%

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The hemoglobin adduct N-(2,3-dihydroxypropyl)-valine as biomarker of dietary exposure to glycidyl esters: a controlled exposure study in humans

et al. 2018

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Fatty acid esters of glycidol (glycidyl esters) are heat-induced food contaminants predominantly formed during industrial deodorization of vegetable oils and fats. After consumption, the esters are digested in the gastrointestinal tract, leading to a systemic exposure to the reactive epoxide glycidol. The compound is carcinogenic, genotoxic and teratogenic in rodents, and rated as probably carcinogenic to humans (IARC group 2A). Assessment of exposure from occurrence and consumption data is difficult, as lots of different foods containing refined oils and fats may contribute to human exposure. Therefore, assessment of the internal exposure using the hemoglobin adduct of glycidol, N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val), may be promising, but a proof-of-principle study is needed to interpret adduct levels with respect to the underlying external exposure. A controlled exposure study was conducted with 11 healthy participants consuming a daily portion of about 36 g commercially available palm fat with a relatively high content of ester-bound glycidol (8.7 mg glycidol/kg) over 4 weeks (total amount 1 kg fat, individual doses between 2.7 and 5.2 µg/kg body weight per day). Frequent blood sampling was performed to monitor the 2,3-diHOPr-Val adduct levels during formation and the following removal over 15 weeks, using a modified Edman degradation and ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/ MS). Results demonstrated for the first time that the relatively high exposure during the intervention period was reflected in corresponding distinct increases of 2,3-diHOPr-Val levels in all participants, following the expected slope for hemoglobin adduct formation and removal over time. The mean adduct level increased from 4.0 to 12.2 pmol 2,3-diHOPr-Val/g hemoglobin. By using a nonlinear mixed model, values for the adduct level/dose ratio (k, mean 0.082 pmol 2,3-diHOPr-Val/g hemoglobin per µg glycidol/kg body weight) and the adduct lifetime (τ, mean 104 days, likely the lifetime of the erythrocytes) were determined. Interindividual variability was generally low. 2,3-DiHOPr-Val was therefore proven to be a biomarker of the external dietary exposure to fatty acid esters of glycidol. From the background adduct levels observed in our study, a mean external glycidol exposure of 0.94 µg/kg body weight was estimated. This value is considerably higher than current estimates for adults using occurrence and consumption data of food. Possible reasons for this discrepancy are discussed (other oral or inhalational glycidol sources, endogenous formation, exposure to other chemicals also forming the adduct 2,3-diHOPr-Val). Further research is necessary to clarify the issue. KeywordsGlycidol · Edman degradation · Protein adduct · Biomarker · Exposure study Abbreviations DHP-Val-FTH N-(2,3-Dihydroxypropyl)-valine fluorescein thiohydantoin 2,3-diHOPr-Val N-(2,3-Dihydroxypropyl)-valine FITC Fluorescein-5-isothiocyanate FTH Fluorescein thiohydantoin Hb Hemoglogin MRM Multiple reaction monitoring T 25Dose...

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A comparison of the exposure system of glycidol‐related chemicals on the formation of glycidol‐hemoglobin adducts

Shimamura,

Wada,

Tashiro

et al. 2023

Food Science & Nutrition

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Glycidol fatty acid esters that are present in foods are degraded in vivo to the animal carcinogen glycidol, which binds to the N‐terminal valine of hemoglobin (Hb) to form N‐(2,3‐dihydroxypropyl)valine (diHOPrVal) adducts. The existence of other chemicals that are converted to glycidol is unknown. To determine the effect of different exposure conditions on the formation of diHOPrVal adducts, several glycidol‐related chemicals (3‐monochloropropane‐1,2‐diol; 3‐MCPD, epichlorohydrin, glyceraldehyde, acrylic acid, and 1,2‐propanediol) were evaluated using in vitro and in vivo (single/repeated dose) methods. In vitro, the reaction of 3‐MCPD or epichlorohydrin with human Hb produced 17% and 0.7% of diHOPrVal, as compared to equimolar glycidol, respectively. Following a single administration of glycidol‐related compounds to ICR mice, diHOPrVal formation was observed only in the epichlorohydrin‐treated group after day 5 of exposure. After 14 days of repeated dosing, the amounts of diHOPrVal produced by epichlorohydrin and 3‐MCPD in vivo were <1% of diHOPrVal produced by an equal molar concentration of glycidol. Furthermore, glyceraldehyde group produced 0.2% of diHOPrVal at the same molar concentration of glycidol equivalents, in which diHOPrVal formation could not be confirmed by the in vitro assay. The results indicate the usefulness of diHOPrVal as an exposure marker for glycidol; however, the contribution of its formation in vivo by exposure to various chemicals will be necessary to validate and interpret the results.

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Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts

Cited by 34 publications

References 24 publications

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

Risks for human health related to the presence of 3‐ and 2‐monochloropropanediol (MCPD), and their fatty acid esters, and glycidyl fatty acid esters in food

The hemoglobin adduct N-(2,3-dihydroxypropyl)-valine as biomarker of dietary exposure to glycidyl esters: a controlled exposure study in humans

A comparison of the exposure system of glycidol‐related chemicals on the formation of glycidol‐hemoglobin adducts

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