Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F1 mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide

Tareke, Eden; Twaddle, Nathan C.; McDaniel, L. Patrice; Churchwell, Mona I.; Young, John F.; Doerge, Daniel R.

doi:10.1016/j.taap.2006.07.013

Cited by 57 publications

(59 citation statements)

References 40 publications

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“…Both parameters are proposed biomarkers of internal acrylamide exposure in humans (22,27,36), but it remains uncertain how closely they are linked to formation of tissue DNA adducts. In rodent studies, a good linear correlation was reported between glycidamide adducts to hemoglobin and liver glycidamide DNA adducts (16) and between acrylamide adducts to hemoglobin and acrylamide sperm DNA adducts (63). However, although the epoxide glycidamide is considered as the ultimate genotoxic agent, there may also be a direct risk caused by acrylamide, which may be as important as that conferred by glycidamide because glycidamide formation is not the main metabolic pathway of acrylamide.…”

Section: Discussionmentioning

confidence: 99%

“…The extent of glycidamide formation is dose and route dependent and it is highest for low-dose dietary acrylamide exposure (15,16). Glycidamide is considered to be more genotoxic and carcinogenic than acrylamide itself (3,(16)(17)(18). In mice, the conversion of acrylamide to glycidamide is mediated by cytochrome P450 2E1 (CYP2E1; refs.…”

Section: Introductionmentioning

confidence: 99%

“…Based on urinary excretion data and levels of acrylamide and glycidamide adducts to hemoglobin, the extent of glycidamide formation and the estimated internal exposure to glycidamide, which is considered to play the main role in acrylamide carcinogenicity (16)(17)(18), are about two to four times lower in humans compared with rodents (9,10). In humans, the urinary concentration ratio of AAMA and GAMA, which is considered as a metric to describe the extent of conversion of acrylamide to glycidamide (9) and thus reflects internal exposure, varies considerably between subjects (22,23).…”

Section: Introductionmentioning

confidence: 99%

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In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Doroshyenko

Fuhr

Kunz

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Acrylamide, a potential food carcinogen in humans, is biotransformed to the epoxide glycidamide in vivo. Both acrylamide and glycidamide are conjugated with glutathione, possibly via glutathione-S-transferases (GST), and bind covalently to proteins and nucleic acids. We investigated acrylamide toxicokinetics in 16 healthy volunteers in a four-period change-over trial and evaluated the respective role of cytochrome P450 2E1 (CYP2E1) and GSTs. Participants ingested selfprepared potato chips containing acrylamide (1 mg) without comedication, after CYP2E1 inhibition (500 mg disulfiram, single dose) or induction (48 g/d ethanol for 1 week), and were phenotyped for CYP2E1 with chlorzoxazone (250 mg, single dose). Unchanged acrylamide and the mercapturic acids N -acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S -(2-hydroxy-2-carbamoylethyl)-cysteine (GAMA) accounted for urinary excretion [geometric mean (percent coefficient of variation)] of 2.9% (42), 65% (23), and 1.7% (65) of the acrylamide dose in the reference period.Hemoglobin adducts increased clearly following the acrylamide test-meal. The cumulative amounts of acrylamide, AAMA, and GAMA excreted and increases in AA adducts changed significantly during CYP2E1 blockade [point estimate (90% confidence interval)] to the 1.34-fold (1.14-1.58), 1.18-fold (1.02-1.36), 0.44-fold (0.31-0.61), and 1.08-fold (1.02-1.15) of the reference period, respectively, but were not changed significantly during moderate CYP2E1 induction. Individual baseline CYP2E1 activity, CYP2E1*6, GSTP1 313A>G and 341T>C single nucleotide polymorphisms, and GSTM1-and GSTT1-null genotypes had no major effect on acrylamide disposition. The changes in acrylamide toxicokinetics upon CYP2E1 blockade provide evidence that CYP2E1 is a major but not the only enzyme mediating acrylamide epoxidation in vivo to glycidamide in humans. No obvious genetic risks or protective factors in xenobiotic-metabolizing enzymes could be determined for exposed subjects. (Cancer Epidemiol

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Doroshyenko

Fuhr

Kunz

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…A formed A-Hb, GA-Hb and GA-DNA adduct. 19 A is dissolved in water very well and distributed to all the tissues in a rapidly after being taken orally and induced hematological and neurotoxic changes in animals. 20 The hemoglobin (Hb) is linked to the total population of red blood cells, the present study revealed that Hb decreased significantly after A administration in rats which might be either due to the retarded synthesis or destruction hemoglobin.…”

Section: Discussionmentioning

confidence: 99%

Protective Role of Kaempferol Against Acrylamide Intoxication

Shrivastava

Uthra

Reshi

et al. 2016

FRA

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“…) drinking water exposures (Tareke et al, 2006;Doerge et al, 2005b). The daily average serum concentrations of AA and GA in rats following a single dose of AA in diet and following three weeks' exposure to AA in drinking water are remarkably similar when normalized to dose, yielding average serum concentrations of both AA and GA of 0.65 μM in blood per mg kg −1 day −1 administered dose.…”

Section: Acrylamidementioning

confidence: 96%

Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context

Hays

Aylward²

2008

J of Applied Toxicology

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Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biological media in persons from the general population. Such data are being generated by biomonitoring programs conducted by the US Centers for Disease Control and other researchers. However, few screening tools are available for interpretation of such data in a health risk assessment context. This review describes the concept and implementation of Biomonitoring Equivalents (BEs), estimates of the concentration of a chemical or metabolite in a biological medium that is consistent with an existing exposure guidance value such as a tolerable daily intake or reference dose. The BE approach integrates available pharmacokinetic data to convert an existing exposure guidance value into an equivalent concentration in a biological medium. Key concepts regarding the derivation and communication of BE values resulting from an expert workshop held in 2007 are summarized. BE derivations for four case study chemicals (toluene, 2,4-dichlorophenoxyacetic acid, cadmium and acrylamide) are presented, and the interpretation of biomonitoring data for these chemicals is presented using the BE values. These case studies demonstrate that a range of pharmacokinetic data and approaches can be used to derive BE values; fully developed physiologically based pharmacokinetic models, while useful, are not required. The resulting screening level evaluation can be used to classify these compounds into relative categories of low, medium and high priority for risk assessment follow-up. Future challenges related to the derivation and use of BE values as tools in risk management are discussed.

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Relationships between biomarkers of exposure and toxicokinetics in Fischer 344 rats and B6C3F1 mice administered single doses of acrylamide and glycidamide and multiple doses of acrylamide

Cited by 57 publications

References 40 publications

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

In vivo Role of Cytochrome P450 2E1 and Glutathione-S-Transferase Activity for Acrylamide Toxicokinetics in Humans

Protective Role of Kaempferol Against Acrylamide Intoxication

Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context

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