Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole

A.M. Alajlouni, A.J. Al-Malahmeh, Reiko Kiwamoto, Sebastiaan Wesseling, A.E.M.F. Soffers, A.A.A. Al-Subeihi, Jacques Vervoort, I.M.C.M. Rietjens

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Abstract

The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10-5 mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.

Original languageEnglish
Pages (from-to)138-150
JournalFood and Chemical Toxicology
Volume89
DOIs
Publication statusPublished - 1 Mar 2016

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Safrole
safrole
Petroselinum
parsley
Risk assessment
risk assessment
mechanism of action
kinetics
Food
Kinetics
neoplasms
Tumors
Animal Testing Alternatives
animal use alternatives
Benchmarking
average daily intake
Neoplasms
carcinogenicity
risk management
Risk Management

Keywords

  • Apiol
  • Margin of exposure
  • PBK modelling
  • Read-across
  • Risk assessment
  • Safrole

Cite this

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title = "Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole",
abstract = "The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10{\%} extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10-5 mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.",
keywords = "Apiol, Margin of exposure, PBK modelling, Read-across, Risk assessment, Safrole",
author = "A.M. Alajlouni and A.J. Al-Malahmeh and Reiko Kiwamoto and Sebastiaan Wesseling and A.E.M.F. Soffers and A.A.A. Al-Subeihi and Jacques Vervoort and I.M.C.M. Rietjens",
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Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole. / Alajlouni, A.M.; Al-Malahmeh, A.J.; Kiwamoto, Reiko; Wesseling, Sebastiaan; Soffers, A.E.M.F.; Al-Subeihi, A.A.A.; Vervoort, Jacques; Rietjens, I.M.C.M.

In: Food and Chemical Toxicology, Vol. 89, 01.03.2016, p. 138-150.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Mode of action based risk assessment of the botanical food-borne alkenylbenzene apiol from parsley using physiologically based kinetic (PBK) modelling and read-across from safrole

AU - Alajlouni, A.M.

AU - Al-Malahmeh, A.J.

AU - Kiwamoto, Reiko

AU - Wesseling, Sebastiaan

AU - Soffers, A.E.M.F.

AU - Al-Subeihi, A.A.A.

AU - Vervoort, Jacques

AU - Rietjens, I.M.C.M.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10-5 mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.

AB - The present study developed physiologically-based kinetic (PBK) models for the alkenylbenzene apiol in order to facilitate risk assessment based on read-across from the related alkenylbenzene safrole. Model predictions indicate that in rat liver the formation of the 1'-sulfoxy metabolite is about 3 times lower for apiol than for safrole. These data support that the lower confidence limit of the benchmark dose resulting in a 10% extra cancer incidence (BMDL10) that would be obtained in a rodent carcinogenicity study with apiol may be 3-fold higher for apiol than for safrole. These results enable a preliminary risk assessment for apiol, for which tumor data are not available, using a BMDL10 value of 3 times the BMDL10 for safrole. Based on an estimated BMDL10 for apiol of 5.7-15.3 mg/kg body wt per day and an estimated daily intake of 4 × 10-5 mg/kg body wt per day, the margin of exposure (MOE) would amount to 140,000-385,000. This indicates a low priority for risk management. The present study shows how PBK modelling can contribute to the development of alternatives for animal testing, facilitating read-across from compounds for which in vivo toxicity studies on tumor formation are available to compounds for which these data are unavailable.

KW - Apiol

KW - Margin of exposure

KW - PBK modelling

KW - Read-across

KW - Risk assessment

KW - Safrole

U2 - 10.1016/j.fct.2016.01.018

DO - 10.1016/j.fct.2016.01.018

M3 - Article

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SP - 138

EP - 150

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

SN - 0278-6915

ER -