“Composition-based risk (and benefit) assessment. Part II- Exercises” · SESSION :Risk and benefit assessment “Composition-based risk (and benefit) assessment. Part II- Exercises”

SESSION :Risk and benefit assessment

“Composition -based risk (and benefit) assessment. Part II- Exercises ”

BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)

Antonella Guzzon, Hylobates

1. Case study: cinnamon bark essential oil

Open collaboration: the RBA

methodology will be freely

accessible through a web

tool (Opasnet).

Advantage: open for

consultation to experts and

policy makers, transparency

1. Case study: cinnamon bark essential oil

Composition of cinnamon essential oil extracted bysteam distillation

1. Systematic literature search

on Pubmed to integrate data

from European Pharmacopeia and

existing assessments.

2. Selection of articles based on

Inclusion/Exclusion criteria�

Only articles reporting the full

composition were used (11 out of

171)


1. Data on composition were

imported in Opasnet and the on-

line tool applied to estimate

mean, median, range of variation


19 compounds identified

Main compound present:

cinnamaldehyde

Risk assessement :- identification and characterisation of adverse health effects- history of consumption and case reports

Methodology is based on 3 steps:

1. data on adverse health effects were collected from relevant authoritative assessments and integrated with literature search on Pubmed.

2. assessment of all data available on the whole preparation and its individual constituents,

3. health guidance values, reference doses and threshold of toxicological concern were used to focus the assessment on compounds that are not unlikely to pose a risk to health.

Identification and characterisation of adverse health effects

Identification and characterisation of adverse health

effects

Online tool for estimating the risk

Intake calculations

• These equations are used to calculate intakes and level of concern:– intakecomp (mg /kg /d) = intake (g /d) * conccomp

(mg /g) / 60 (kg)– concern indicatorcomp,i = intakecomp (mg /kg /d)

/ guidance valuecomp,i (mg /kg /d) * safety factori

• comp = index for compounds• i = index for indicators

4 compound above health guidance valuesCaryophyllene,Cinnamyl acetate,Para-methoxycinnamaldehyde,Safrole

11 compounds above health guidance values2-Carene, Cadinene, Caryophyllene, Cinnamaldehyde, Cinnamyl acetate, Para-methoxycinnamaldehyde, Safrole, Trans-2-methoxycinnamaldehyde, Z-cinnamaldehyde, Alpha-copaene, Alpha-muurolene

Lowest intake of essential oil:50 mg/day

Highest intake of essential oil:200 mg/day




Case reports of adverse effects

23 reported adverse cases:

majority due to the consumption

(chronic use) of chewing-gums

and cosmetics.

Few cases for food supplements.

Case reports of adverse effects

EMA reported oral mucosal

inflammation and lesions following

consumption of cinnamon flavored

chewing gums.

Effects reported were not severe and

reversible.

Likelihood of adverse effects from

cinnamon used in food supplement

lower than cinnamon used in chewing

gums or cosmetics.

No human studies available that

might have detected adverse events.

Vienna – 5th Project Meeting- May 13th 2014

BRASOV PROJECT MEETINGS - MAY 2011

Beneficial effects of cinnamon

essential oil were identified

based on benefits indicated in

the Italian list of approved plants

and acknowledeged by EFSA as

physiological beneficial effects

Benefit assessement

Vienna – 5th Project Meeting- May 13th 2014Vienna – 5th Project Meeting- May 13th 2014

Benefit assessement

Reduction of flatulence and bloatingData from traditon of use and in vitro studiesNon data from in vivo animal studies or human studies

Benefit assessement

Maintenance of normal blood glucose concentrationData from traditon of use, in vitro studies, in vivo animal studies . No data from human studies.

Evaluation of quality and strength of the evidence

based on WHO approach (2003) modified considering that forbotanical prearation evidence is available from tradition of use, in vitro, in vivo, human data

Evaluation of quality and strength of the evidence

Risk and benefit characterisation

Long history of consumption. Unlinkely sever and non-reversible acute

adverse effects.Additional toxicological data would be required for some

compounds to reduce uncertainty.

Considerable uncertainty on the benefits. Tradition is convincing while there

is imited in vitro and in vivo evidence, no human data

Benefits are unlikely to outweigh risks. Risks are expected to be low, but

uncertainty exist (safrole levels, extent of chronic consumption, maximum

intake levels)

1. Literature data data on

composition were collected and

imported in Opasnet and tool

applied to estimate mean,

median, range of variation

2. Case study: bitter fennel, dried seeds, essential oil

Composition of fennel dried fruits essential oil

Main compounds found:

Trans-anethole

Eugenol

Estragole

Almost all the compounds were present in concentration below the related health guidance values or toxicological threshold of concern except for apiole and estragole. Estragole in some cases was found in high concentrations� genotoxic compound

Identification and characterisation of adverse health e ffects

Supplements containing fennel essential oil (median intake e.o. 0.28 mg/day)

Supplements containing powdered seeds (median intake 102.25 mg/day)

3. Case study: Ginkgo biloba, dried leaf extract

Various compounds were found:the most abundant were quercitin(9.31%) and bilobalide (2.9%)


� Bilobalide is the onlycompound present inconcentrations higher than thesafety level.

� It might represent a priority forthe risk assessment due toconsumption of Ginkgo biloba.

� Further studies would beneeded to confirm theconcentration of thecompound.

Compos

to

Media Sd Min Q0.025 Median

a

Q0.075 Max

1 Bilobalide 14.06 9.98 0.00 0.00 20.40 21.80 21.80


Overall conclusions

� Integrated approach to risk-benefit assessment of PFSs was developed and applied to case-studies in the Opasnet platform.

� Opasnet: collaborative and transparent approach.

� Assessments structured in different pages corresponding to the steps of the RBA methodology

Overall conclusions

� Exposure assessment: database with literature data wascreated. It is possible to estimate mean, median,percentiles of intake of each compound for eachextraction.

� Online tool for estimating the risk of single compoundsbased on concentration data and intake levels.

“Composition-based risk (and benefit) assessment. Part II- Exercises” · SESSION :Risk and benefit assessment “Composition-based risk (and benefit) assessment. Part II- Exercises”

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