foodchemicalsafety brett jeffery

7/29/2019 FoodChemicalSafety Brett Jeffery

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Food Chemical Safety An industry perspective

Brett Jeffery

1st March 2011


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Food Chemical Safety

Definitions

Chemical Hazards

Risk Assessment

Hazard identification

Dose response

Exposure assessment


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DefinitionsHazardInherent property of an agent or situation having the potential to cause adverse effectswhen an organism, system or (sub) population is exposed to that agent.ExposureConcentration or amount of a particular agent that reaches a target organism, system

or (sub) population in a specific frequency for a defined duration.

RiskThe probability of an adverse effect in an organism, system or (sub) population causedunder specified circumstances by exposure to an agent.


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Risk AssessmentFour steps:


Hazard characterisation (dose response relationship)

Exposure assessment

Risk characterisation (compared with exposure level)


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Risk characterisation Simply put:

an estimate of the probability that an adverse health effect will occurrence following exposure to

a chemical at a particular exposure level

Risk management Decision-making process - involving considerations of political, social, economic, and technical

factors

Include risk assessment

Should be kept separate from risk assessment


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Chemical HazardsNaturally occurring

e.g. mycotoxins, shellfish toxins, plant toxins.

Man made e.g.dioxins, heavy metals, pesticide residues.

Process related e.g. acrylamide, furans, 3-MCPD.

bisphenol A


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Hazards in Pet care productsCore ingredients:

- garlic, lutein.

Micronutrients: - vitamin D

Functional ingredients: .alginate

Contaminants Melamine/cyanuric acid


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Databases available at:http://jecfa.ilsi.org/http://www.who.int/ipcs/food/jecfa/en/www.inchem.orghttp://toxnet.nlm.nih.gov/

Other sources of informationEuropean Food Standards Agency - www.efsa.euUS Food and Drug Administration - www.fda.gov

Contaminant levelsWHO Joint meeting on Pesticides Residues (JMPR) -http://www.who.int/ipcs/publications/jmpr/en/


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Paracelsus (1493-1541)German

"All things are poison and nothing iswithout poison, only the dose permitssomething not to be poisonous."


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Why are chemicals toxic? Dose dependent

acute or chronic

Detoxification mechanisms

Mechanism of action

Receptor mediated

Physical obstruction

Oxidative stress Log10 Dose

Response

LD50


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Why do a toxicological risk assessment? To determine whether there is sufficient data to provide reassurance that there is little likelihood

of adverse health effects occurring under given exposure conditions.

Does not estimate magnitude of risk I.e no of people effected.

Setting intake or exposure levels

Identify compounds that are mutagens, genotoxic carcinogens, e.g. benzene. These are non-

threshold compounds. Requires overall toxicological profile of a chemical.


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Toxicological risk assessmentFour stages

Hazard identification: what are the substances of concern and what are the adverse effects?

Dose (concentration) - response (effect) relationship: Is the a threshold below which no effect isobserved?

Exposure assessment: Intake data, distribution of intake in population, different routes of

exposure.

Risk characterisation: Comparison of a toxicologically derived exposure limit with an exposure

estimate.


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Hazard identificationWhat are the substances of concern and what are the adverse effects?

Physico-chemical properties

e.g. irritant -styrene, corrosive - H2SO4

Acute toxicity - after a single exposure.

Chronic toxicity - repeated exposure over a longer time period.

Reproductive and developmental toxicity

Epidemiology - retrospective case control studies.

Reversible vs.. Irreversible.

e.g. skin irritation, anaesthesia

kidney damage due to Cd, cancer


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Toxicity studies

Derive exposure level e.g. Tolerable Daily Intake (TDI)

In vivo studiesDifferent species - rat, mouse

Different strains - Sprague dawley (rat) /C57BL (mouse)

Route of administrationi.e. oral, intra-venous, intra-peritoneal, sub-cutaneous.

Consider vehicle in which compound is administered e.g solvent


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Acute toxicity and LD50 values LD50: The dose of a toxic compound that causes death in 50% of a group of experimental

animals to which it is administered. It can be used to assess the acute toxicity of a

compound, but is being superseded by more refined methods.

Provides no information on the dose response relationship i.e the LD50 value cannot be usedto derive a NOAEL.

LD50 provides a crude assessment of acute toxicity over a specified time period.

Allow identification of a starting dose in acute oral toxicity studies.


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Class LD50 for the rat (mg/kg body weight)

Oral Dermal

Solids Liquids Solids Liquids

Ia Extremely hazardous 5 or less 20 or less 10 or less 40 or less

Ib Highly hazardous 5-50 20-200 10-100 40-400

II Moderately hazardous 50-500 200-2000 100-1000 400-4000

III Slightly hazardous Over 500 Over 2000 Over 1000 Over 4000

The terms solids and liquids refer to the physical state of the active ingredient being classified.

E.g.,pesticide toxicities have been classified according to oral and dermal LD50values.

Basis of WHO pesticide classification according to LD50values

Acute toxicity and LD50 values

LD50 mg/kg Toxicity class Number of

chemicals

Chemicals (%)

25 1 Very toxic 0 0

> 25 200 2 Toxic 35 3.1> 200- 2000 3 Harmful 235 21.1

> 2000 4 Unclassified 845 75.8

EU Chemical classification (pre-

REACH)


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Types of Exposure LimitAcceptable Daily Intake (ADI):An estimate of the amount of a substance in food or

drinking water, expressed on a body-weight basis, that can be ingested daily over a

lifetime without appreciable risk (standard human = 60 kg). The ADI is listed in units of

mg per kg of body weight.

Tolerable Daily Intake (TDI):An estimate of the amount of contaminant, expressed on a

body weight basis (e.g. mg/kg bodyweight), that can be ingested daily over a lifetime

without appreciable health risk.

An ADI is typically derived for food additives, pesticides and veterinary medicines.

A TDI is derived for chemical contaminants.


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Dose response curve

Log10 Dose

Response

LD50

The LD50 is the mid-point of the dose response curve and thepoint at which the 95% confidence intervals are narrowest.As a result the LD50 value is the most useful for comparison oftoxicity between chemicals

NOAEL


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Derivation of a Exposure LimitFrom in vivostudies identify pivotal study

Select No Observed Adverse Effect Level (NOAEL)

Consider interspecies toxicodynamics - apply x2.5 uncertainty factor

Consider interspecies toxicokinetics - apply x4.0 uncertainty factor

Interspecies variability uncertainty factor is x10 (2.5x4)

Consider human variability in toxicodynamics - apply x3.2 uncertainty factor

Consider human variability in toxicokinetics - apply x3.2 uncertainty factor

Uncertainty factor for variation in human population is x10 (3.2 x 3.2)

Other considerations - nature of toxicity , knowledge gaps in toxicological profile

Use a default overall uncertainty factor of x100

The ADI or TDI is obtained by dividing the critical NOAEL by the overall uncertaintyfactor


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Derivation of a Exposure Limit (companion animals)From in vivostudies identify pivotal study

Select No Observed Adverse Effect Level (NOAEL)

Consider animal variability in toxicodynamics - apply x3.2 uncertainty factor

Consider animal variability in toxicokinetics - apply x3.2 uncertainty factor

Uncertainty factor for variation in human population is x10 (3.2 x 3.2)

Other considerations - nature of toxicity , knowledge gaps in toxicological profile

Apply addition factor of x 10 if limited data available

Use a default overall uncertainty factor of x100

The ADI or TDI is obtained by dividing the critical NOAEL by the overall uncertainty

factor


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Derivation of a Exposure Limit - other considerations Is all the toxicity data available?

Addition uncertainty factor if Lowest Observed Adverse Effect Level is identified (in absence of a

NOAEL).

Is it possible to use data derived uncertainty factors compared to default values?

Is the test species more or less sensitive?

Other approaches Margin of Exposure (MoE) e.g acrylamide

Approach compares estimate of exposure to the critical NOAEL


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Derivation of an Exposure Limit - Examples Ochratoxin A

Last considered by JECFA in 2007 which set a PTWI of 100ng/kg bw

Cyanogenic glycosides

Last considered by UK CoT in March 2006.

Based on limited data the UK CoT concluded that The range for the lethal dose

in humans was 0.5 to 3.5 mg/kg bw/day,applying a 100 fold uncertainty factor to

the lowest lethal dose, to allow for extrapolation from LOAEL to NOAEL and for

inter-individual differences would result in a TDI of 5 mg/kg bw/day.

Dioxin (TCDD)

Last considered by JECFA in 2001 who set a PTMI 70 pg/kg bw


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Exceedance over the Exposure Limit

If exposure is above the level derived from the NOAEL/LOAEL

Indicates potential health concern

Raw material / finished product may be illegal or out of spec.

Food safety risk assessment

Part of Business risk assessment


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What to do in the absence of a specific relevant LD50 value?

Indicative that very little toxicity data is available.

History of safe use

Generally Regarded as Safe (GRAS) status

Novel food?

Regulatory requirements

Insufficient toxicity data - cannot derive exposure limit

Ingredient prohibited from use


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Risk assessment of non-threshold compounds Examples

Lead

Benzene

Vinyl chloride

International Agency for Research of Cancer (IARC)


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Summary Every chemical is toxic at sufficient dose

May occur as a contaminant or naturally occurring chemical

4 steps in risk assessment


Dose response relationship

Exposure assessment

Risk characterisation

Requires toxicity data

Uncertainty factors


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Thank you

foodchemicalsafety brett jeffery

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