Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms

Helle Katrine Knutsen, Lars Barregård, Margherita Bignami, Beat Brüschweiler, Sandra Ceccatelli, Bruce Cottrill, Michael Dinovi, Lutz Edler, Bettina Grasl-Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Carlo Stefano Nebbia, Isabelle Oswald, Annette Petersen, Martin Rose, Alain-Claude Roudot, Tanja Schwerdtle, Christiane Vleminckx, Günter Vollmer, Heather Wallace & 8 others Chiara Dall'Asta, Arno Gutleb, Manfred Metzler, Dominique Parent-Massin, Marco Binaglia, Hans Steinkellner, Jan Alexander, EFSA Panel on Contaminants in the Food Chain (CONTAM)

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Abstract

The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 μg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2 and using a reduction in total leucocyte count as the critical endpoint. An acute reference dose (ARfD) of 0.3 μg for T2 or T2/kg bw was established based on acute emetic events in mink. Modified forms of T2 and HT2 identified are phase I metabolites mainly formed through hydrolytic cleavage of one or more of the three ester groups of T2. Less prominent hydroxylation reactions occur predominantly at the side chain. Phase II metabolism involves conjugation with glucose, modified glucose, sulfate, feruloyl and acetyl groups. The few data on occurrence of modified forms indicate that grain products are their main source. The CONTAM Panel found it appropriate to establish a group TDI and a group ARfD for T2 and HT2 and its modified forms. Potency factors relative to T2 for the modified forms were used to account for differences in acute and chronic toxic potencies. It was assumed that conjugates (phase II metabolites of T2, HT2 and their phase I metabolites), which are not toxic per se, would be cleaved releasing their aglycones. These metabolites were assigned the relative potency factors (RPFs) of their respective aglycones. The RPFs assigned to the modified forms were all either 1 or less than 1. The uncertainties associated with the present assessment are considered as high. Using the established group, ARfD and TDI would overestimate any risk of modified T2 and HT2.
Original languageEnglish
Article numbere04655
JournalEFSA Journal
Volume15
Issue number1
DOIs
Publication statusPublished - 26 Jan 2017

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T-2 Toxin
No-Observed-Adverse-Effect Level
Poisons
Health
Body Weight
Emetics
Mink
Recommended Dietary Allowances
Food Chain
Hydroxylation
Leukocyte Count
Uncertainty
Esters
Glucose

Keywords

  • T2
  • HT2
  • modified forms
  • group health based guidance values

Cite this

Knutsen, H. K., Barregård, L., Bignami, M., Brüschweiler, B., Ceccatelli, S., Cottrill, B., ... EFSA Panel on Contaminants in the Food Chain (CONTAM) (2017). Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms. EFSA Journal, 15(1), [e04655]. https://doi.org/10.2903/j.efsa.2017.4655

Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms. / Knutsen, Helle Katrine ; Barregård, Lars; Bignami, Margherita; Brüschweiler, Beat ; Ceccatelli, Sandra; Cottrill, Bruce; Dinovi, Michael; Edler, Lutz; Grasl-Kraupp, Bettina ; Hogstrand, Christer ; Hoogenboom, Laurentius (Ron) ; Nebbia, Carlo Stefano ; Oswald, Isabelle ; Petersen, Annette ; Rose, Martin ; Roudot, Alain-Claude ; Schwerdtle, Tanja ; Vleminckx, Christiane ; Vollmer, Günter ; Wallace, Heather; Dall'Asta, Chiara; Gutleb, Arno; Metzler, Manfred ; Parent-Massin, Dominique ; Binaglia, Marco ; Steinkellner, Hans ; Alexander, Jan ; EFSA Panel on Contaminants in the Food Chain (CONTAM).

In: EFSA Journal, Vol. 15, No. 1, e04655, 26.01.2017.

Research output: Contribution to journalArticle

Knutsen, HK, Barregård, L, Bignami, M, Brüschweiler, B, Ceccatelli, S, Cottrill, B, Dinovi, M, Edler, L, Grasl-Kraupp, B, Hogstrand, C, Hoogenboom, LR, Nebbia, CS, Oswald, I, Petersen, A, Rose, M, Roudot, A-C, Schwerdtle, T, Vleminckx, C, Vollmer, G, Wallace, H, Dall'Asta, C, Gutleb, A, Metzler, M, Parent-Massin, D, Binaglia, M, Steinkellner, H, Alexander, J & EFSA Panel on Contaminants in the Food Chain (CONTAM) 2017, 'Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms', EFSA Journal, vol. 15, no. 1, e04655. https://doi.org/10.2903/j.efsa.2017.4655
Knutsen HK, Barregård L, Bignami M, Brüschweiler B, Ceccatelli S, Cottrill B et al. Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms. EFSA Journal. 2017 Jan 26;15(1). e04655. https://doi.org/10.2903/j.efsa.2017.4655
Knutsen, Helle Katrine ; Barregård, Lars ; Bignami, Margherita ; Brüschweiler, Beat ; Ceccatelli, Sandra ; Cottrill, Bruce ; Dinovi, Michael ; Edler, Lutz ; Grasl-Kraupp, Bettina ; Hogstrand, Christer ; Hoogenboom, Laurentius (Ron) ; Nebbia, Carlo Stefano ; Oswald, Isabelle ; Petersen, Annette ; Rose, Martin ; Roudot, Alain-Claude ; Schwerdtle, Tanja ; Vleminckx, Christiane ; Vollmer, Günter ; Wallace, Heather ; Dall'Asta, Chiara ; Gutleb, Arno ; Metzler, Manfred ; Parent-Massin, Dominique ; Binaglia, Marco ; Steinkellner, Hans ; Alexander, Jan ; EFSA Panel on Contaminants in the Food Chain (CONTAM). / Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms. In: EFSA Journal. 2017 ; Vol. 15, No. 1.
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abstract = "The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 μg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2 and using a reduction in total leucocyte count as the critical endpoint. An acute reference dose (ARfD) of 0.3 μg for T2 or T2/kg bw was established based on acute emetic events in mink. Modified forms of T2 and HT2 identified are phase I metabolites mainly formed through hydrolytic cleavage of one or more of the three ester groups of T2. Less prominent hydroxylation reactions occur predominantly at the side chain. Phase II metabolism involves conjugation with glucose, modified glucose, sulfate, feruloyl and acetyl groups. The few data on occurrence of modified forms indicate that grain products are their main source. The CONTAM Panel found it appropriate to establish a group TDI and a group ARfD for T2 and HT2 and its modified forms. Potency factors relative to T2 for the modified forms were used to account for differences in acute and chronic toxic potencies. It was assumed that conjugates (phase II metabolites of T2, HT2 and their phase I metabolites), which are not toxic per se, would be cleaved releasing their aglycones. These metabolites were assigned the relative potency factors (RPFs) of their respective aglycones. The RPFs assigned to the modified forms were all either 1 or less than 1. The uncertainties associated with the present assessment are considered as high. Using the established group, ARfD and TDI would overestimate any risk of modified T2 and HT2.",
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author = "Knutsen, {Helle Katrine} and Lars Barreg{\aa}rd and Margherita Bignami and Beat Br{\"u}schweiler and Sandra Ceccatelli and Bruce Cottrill and Michael Dinovi and Lutz Edler and Bettina Grasl-Kraupp and Christer Hogstrand and Hoogenboom, {Laurentius (Ron)} and Nebbia, {Carlo Stefano} and Isabelle Oswald and Annette Petersen and Martin Rose and Alain-Claude Roudot and Tanja Schwerdtle and Christiane Vleminckx and G{\"u}nter Vollmer and Heather Wallace and Chiara Dall'Asta and Arno Gutleb and Manfred Metzler and Dominique Parent-Massin and Marco Binaglia and Hans Steinkellner and Jan Alexander and {EFSA Panel on Contaminants in the Food Chain (CONTAM)}",
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T1 - Appropriateness to set a group health based guidance value for T2 and HT2 toxin and its modified forms

AU - Knutsen, Helle Katrine

AU - Barregård, Lars

AU - Bignami, Margherita

AU - Brüschweiler, Beat

AU - Ceccatelli, Sandra

AU - Cottrill, Bruce

AU - Dinovi, Michael

AU - Edler, Lutz

AU - Grasl-Kraupp, Bettina

AU - Hogstrand, Christer

AU - Hoogenboom, Laurentius (Ron)

AU - Nebbia, Carlo Stefano

AU - Oswald, Isabelle

AU - Petersen, Annette

AU - Rose, Martin

AU - Roudot, Alain-Claude

AU - Schwerdtle, Tanja

AU - Vleminckx, Christiane

AU - Vollmer, Günter

AU - Wallace, Heather

AU - Dall'Asta, Chiara

AU - Gutleb, Arno

AU - Metzler, Manfred

AU - Parent-Massin, Dominique

AU - Binaglia, Marco

AU - Steinkellner, Hans

AU - Alexander, Jan

AU - EFSA Panel on Contaminants in the Food Chain (CONTAM)

N1 - Acknowledgements: The Panel wishes to thank the members of the Working Group on HBGV for mycotoxins and their modified forms: Jan Alexander, Chiara Dall'Asta, Arno Gutleb, Manfred Metzler, Isabelle Oswald and Dominique Parent-Massin for the preparatory work on this scientific opinion, and the EFSA staff members: Marco Binaglia and Hans Steinkellner for the support provided to this scientific opinion.

PY - 2017/1/26

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N2 - The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 μg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2 and using a reduction in total leucocyte count as the critical endpoint. An acute reference dose (ARfD) of 0.3 μg for T2 or T2/kg bw was established based on acute emetic events in mink. Modified forms of T2 and HT2 identified are phase I metabolites mainly formed through hydrolytic cleavage of one or more of the three ester groups of T2. Less prominent hydroxylation reactions occur predominantly at the side chain. Phase II metabolism involves conjugation with glucose, modified glucose, sulfate, feruloyl and acetyl groups. The few data on occurrence of modified forms indicate that grain products are their main source. The CONTAM Panel found it appropriate to establish a group TDI and a group ARfD for T2 and HT2 and its modified forms. Potency factors relative to T2 for the modified forms were used to account for differences in acute and chronic toxic potencies. It was assumed that conjugates (phase II metabolites of T2, HT2 and their phase I metabolites), which are not toxic per se, would be cleaved releasing their aglycones. These metabolites were assigned the relative potency factors (RPFs) of their respective aglycones. The RPFs assigned to the modified forms were all either 1 or less than 1. The uncertainties associated with the present assessment are considered as high. Using the established group, ARfD and TDI would overestimate any risk of modified T2 and HT2.

AB - The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for T2 and HT2 of 0.02 μg/kg body weight (bw) per day based on a new in vivo subchronic toxicity study in rats that confirmed that immune- and haematotoxicity are the critical effects of T2 and using a reduction in total leucocyte count as the critical endpoint. An acute reference dose (ARfD) of 0.3 μg for T2 or T2/kg bw was established based on acute emetic events in mink. Modified forms of T2 and HT2 identified are phase I metabolites mainly formed through hydrolytic cleavage of one or more of the three ester groups of T2. Less prominent hydroxylation reactions occur predominantly at the side chain. Phase II metabolism involves conjugation with glucose, modified glucose, sulfate, feruloyl and acetyl groups. The few data on occurrence of modified forms indicate that grain products are their main source. The CONTAM Panel found it appropriate to establish a group TDI and a group ARfD for T2 and HT2 and its modified forms. Potency factors relative to T2 for the modified forms were used to account for differences in acute and chronic toxic potencies. It was assumed that conjugates (phase II metabolites of T2, HT2 and their phase I metabolites), which are not toxic per se, would be cleaved releasing their aglycones. These metabolites were assigned the relative potency factors (RPFs) of their respective aglycones. The RPFs assigned to the modified forms were all either 1 or less than 1. The uncertainties associated with the present assessment are considered as high. Using the established group, ARfD and TDI would overestimate any risk of modified T2 and HT2.

KW - T2

KW - HT2

KW - modified forms

KW - group health based guidance values

U2 - 10.2903/j.efsa.2017.4655

DO - 10.2903/j.efsa.2017.4655

M3 - Article

VL - 15

JO - EFSA Journal

JF - EFSA Journal

SN - 1831-4732

IS - 1

M1 - e04655

ER -