NanoRelease Food Additive Task Group 3 White Paper

NanoRelease Food AdditiveTask Group 3 White Paper

Current Findings and ConclusionsApril 16, 2013

- Alimentary Canal Models-

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The statements made in this presentation reflect the personal scientific opinion of the co-chairs and co-authors, and do not necessarily reflect the official position of any of the employers or organizations affiliated with the co-chairs and co-authors.

The recommendations do not supersede applicable national legal risk assessment requirements. They will not necessarily be used as a basis for guidelines and/or recommendations issued by regulatory authorities.

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Disclaimer



Task Group 3 - Aim

We aimed to prepare a review of alimentary canal models applicable for the assessment of the stability, kinetics, bioavailability and excretion of engineered nanomaterials following release from food.



TG3: Alimentary Canal ModelsMEMBERS


Vicki Stone (COCHAIR) Heriot-Watt Univ. Jayadev Raju Health Canada

Rekha Mehta (COCHAIR) Health Canada Koen Venema TNO Netherlands

Eva-Maria Collnot (COCHAIR) Saarland Univ. Lourdes Gombau Leitat Tech Center

Alastair Watson Univ. of East Anglia Luis Valerio US Food and Drug Admin.

Amy Clippinger PETA Paul Singh Univ. of California Davis

David Lefebvre (presenting) Health Canada Jonathan Powell

(advisor)MRC Human

Nutrition Research

Genevieve Bondy Health Canada Susann Bellman (advisor) TNO Netherlands

Hans Bouwmeester RIKILT Inst. of Food Safety


Table of ContentsChapter 1: Introduction

Chapter 2: Applicability of models of the healthy alimentary canal

Chapter 3: Applicability of models for physiological and disease states of the alimentary canal

Chapter 4: Specific examples of nanomaterial quantification in models of the alimentary canal

Chapter 5: Discussion and Conclusions

(100 pages)



Model Categories

• In vivo

• Ex vivo

• In vitro

• In silico



The 3 categories can be studied in these systems• soft/lipid-based nanomaterials• solid non-lipid non metal nanomaterials• solid metalloid / metal-based nanomaterials

• Several examples of each are available in the literature. No clear tendencies are yet apparent. Stability, kinetics, bioavailability and excretion rates can vary depending on specific nanomaterial surface chemistry, size, charge, etc.

• Controls: ions, nanomaterials, bulk material

Discussion of Findings



Recommendations on models of the alimentary canal for assessment of

the stability, behaviour, bioavailability and excretion of nanomaterials

following release from food



TIER 1Screen the nanomaterial in the following systems to quantify stability, solubility, agglomeration, and dynamics such as absorption and movement along the alimentary canal towards fecal excretion.

• In silico computational models built on analytical data with similar nanomaterials – if such data is available for comparison

• In vitro non-cellular digestive fluids to model conditions in the mouth, stomach, small intestine and/or large intestine



TIER 2Reconstruct healthy intestine using cells In Vitro:• Epithelial cells of the buccal cavity (mouth)• Intestinal Caco-2 enterocyte-like cells• Co-culture to generate intestinal M-cells• Co-culture with mucus-producing cells

Some in vitro models can be adapted to reflect disease states. If a subpopulation of humans has a physiological state which modifies their ability to absorb nutrients or toxins, bioavailability could also be studied in these disease models. An alternative would be the use of inter-individual uncertainty factors.



TIER 3In Vivo studies in wild-type rodents and/or rodent models of human diseases. Use OECD oral exposure and toxicokinetic protocols.

This tier could be important for engineered nanomaterials which will have high human exposure levels.

An interspecies uncertainty factor is sometimes used to relate data in animals to human risk assessment.


Notes on the Recommendations

•Relevant models exist. However, the alternative models require standardization and validation before being acceptable for all stakeholders.

•There likely won’t be a single method that addresses all of the necessary questions.


Methods Development Needs

• Development of analytical tools to quantify nanomaterial stability in complex media, saliva, chyme, feces and biological tissues; for assessment of the kinetics of food-borne nanomaterials

• Validation of existing absorption and excretion models for use in risk assessment of nanomaterials (particularly confirmation that alternative ex vivo, in vitro and in silico models are reflective of animals and humans).


Factors to consider in the selection of alimentary canal models for

further development

• reproducibility• ease of use• time required• easy access to required instrumentation,

reagents and expertise• cost-effectiveness


Task Group 3 White Paper Status

• We are in the final stages of drafting

• We are open to input from stakeholders on our suggested tiered approach to the selection of models of the alimentary canal


Thank you for your attention!


NanoRelease Food Additive Task Group 3 White Paper

Documents

alimentary canal chapter

applicability of models

excretion of nanomaterials

silico computational

fecal excretion

excretion rates

similar nanomaterials

healthy intestine