Is my food safe A beginner's guide to risk by gyp13052

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									                              School of Medicine,
                              University of Southampton




             Is my food safe?
A beginner’s guide to risk assessment

                       by
                Andrew G Renwick

Emeritus Professor          Tel 023 8059 5210
School of Medicine
University of Southampton
                            Fax 023 8059 4262
Bassett Crescent East       Email agr@soton.ac.uk
Southampton SO16 7PX
                              School of Medicine,
                              University of Southampton




     What do we mean by
           “safe”?
                      by
                Andrew G Renwick

Emeritus Professor          Tel 023 8059 5210
School of Medicine
University of Southampton
                            Fax 023 8059 4262
Bassett Crescent East       Email agr@soton.ac.uk
Southampton SO16 7PX
What do we mean by safe?
In lay terms “safe” would be interpreted as an
absence of harm – i.e. it is an absolute term
equivalent to “zero risk”

Using this definition – Is my food safe?   “NO”

Nothing in life is absolutely safe
– everything essential for life is harmful when
  taken in excess
– for example salt, oxygen, vitamin A etc can
  produce adverse effects at only slightly
  increased intake levels
“All things are toxic and there is
nothing without poisonous
qualities: it is only the dose which
makes something a poison”




              PARACELSUS (1493-1541)
Scientific definition of “Safety”
The high probability that injury will not result
from exposure to a substance under defined
conditions of quantity and manner of use, ideally
controlled to minimize exposure a
Using this definition – Is my food safe?      “NO”




           a – Fundamental Toxicology – Duffus and Worth
The main risks are microbial contamination and
our “normal” excessive intakes of calories, fat,
cholesterol, salt, red meat etc,
In addition, food contains many “natural” potentially toxic
chemicals:-
Plants – growth hormones, phytoestrogens, alkaloids etc
Fungi – mycotoxins such as aflatoxin, ochratoxin A, etc
Bacteria – various toxins and secondary metabolites
Geological – toxic metals
Pyrolysis products – acrylamide, arylamines etc
In contrast, “man-made” chemicals that are used
in food production and processing, such as
pesticides and food additives, are thoroughly
tested and carefully controlled
   Are pesticide residues safe?
  A beginner’s guide to risk assessment

1. What is risk assessment?
2. How does the PRC use risk assessment?
3. Does the PRC take account of the latest
   science?
4. Does the PRC consider combined intakes (the
   "cocktail effect")?
   Are pesticide residues safe?
  A beginner’s guide to risk assessment

1. What is risk assessment?
2. How does the PRC use risk assessment?
3. Does the PRC take account of the latest
   science?
4. Does the PRC consider combined intakes (the
   "cocktail effect")?
THE RISK ASSESSMENT PARADIGM
1. HAZARD IDENTIFICATION
        What can it do?

2. HAZARD CHARACTERISATION
        What is the dose-response?
        What would be a “safe” dose for humans?

3. INTAKE ASSESSMENT
        What is the intake by humans?

4. RISK CHARACTERISATION
        What is the risk associated with that intake?
    HAZARD
 IDENTIFICATION


    HAZARD           EXPOSURE
CHARACTERISATION    ASSESSMENT


              RISK
        CHARACTERISATION


     RISK                RISK
  MANAGEMENT         COMMUNICATION
         An inherent property of the molecule -
HAZARD   which does not take dose-response
         into account

         The likelihood of that property being
RISK     expressed - under relevant exposure
         conditions
CHEMICAL RISK ASSESSMENT
The current methods to assess the risk to human
health were established about 50 years ago
The approaches used by PSD, ACP and PRC are
the same as those used by
WHO – JMPR and JECFA
EFSA – additives, pesticides and contaminants
FSA – e.g. COT and COC
The methods evolve as the science progresses
All available data on a chemical are considered in
a structured approach
HAZARD IDENTIFICATION
               Various genetic endpoints in bacteria and mammalian cells;
Genetic
               screen for potential carcinogens

Acute          Usually single dose study

               Repeated daily doses for 14-28 days; identifies the target
Short-term     organ

               Repeated daily doses for 90 days; gives dose-response, and
Sub-chronic    used for dose selection in chronic studies

               Repeated daily doses for two years in rodents; used to
Chronic        investigate carcinogenicity; usual source of NOAEL for ADI

               Dosing occurs before during and after reproduction to
Reproductive   investigate effects on foetal and neonatal development

A comprehensive safety/toxicology database is required
on a pesticide before it is approved – therefore we know
about the relevant hazards – but what are the risks?
HAZARD CHARACTERISATION
All animals (including humans) have always been exposed
to potentially toxic chemicals
Adverse effects arise when a stimulus exceeds the normal
homeostatic mechanisms that protect cells
Normal homeostatic processes prevent or reverse any
tendency to change at low exposures – therefore there is
no response
Once a hazard has been defined it is possible to define an
exposure that does NOT produce that effect
HAZARD CHARACTERISATION

THRESHOLD EFFECTS
Analyse dose-response data to define most sensitive
toxic effect - that produced at the lowest doses in the
most sensitive species
Define a daily intake that does NOT produce that effect
– the no-observed-adverse-effect levels (NOAEL)
                                            100
                                            90

Dose-response in animals                    80
                                            70
                               % Response   60
                                            50
                                            40
                                                    NOAEL
                                            30
                                            20
                                            10
                                             0
                                              0.1     1            10    100
                                                      Dose (mg/kg/day)
HAZARD CHARACTERISATION

THRESHOLD EFFECTS
Analyse dose-response data to define most sensitive
toxic effect - that produced at the lowest doses in the
most sensitive species
Define a daily intake that does NOT produce that effect

A health-based intake limit (or “safe intake”) is
determined by dividing the experimental no-observed-
adverse-effect levels (NOAELs) in the most sensitive
animal studies (for long-term or short-term intake) by
an uncertainty factor to allow for species differences
and human variability
                                           100
                                            90

Dose-response in animals                    80
                                            70




                              % Response
                                            60
                                            50
                                            40
                                                          NOAEL
                                            30
                                            20
                                            10
                                             0
                                              0.1               1             10        100
                                                                Dose (mg/kg/day)


                                                                           Divide NOAEL by
                                                                           safety or uncertainty
                                                                           factors
“Safe” intake for humans                   100
                                           90
                                           80
                                           70
                           % Response

                                           60
                                           50       ADI
                                           40
                                           30
                                           20
                                           10
                                            0
                                             0.01         0.1          1           10   100

                                                                Dose (mg/kg/day)
The use of uncertainty or safety factors

            SPECIES            HUMAN
            DIFFERENCES        VARIABILITY




              10                 10


 A 100-fold uncertainty or safety factor has
 been used by bodies such as WHO, SCF/EFSA,
 FDA, FSA and COT for the past 50 years to
 extrapolate from a group of test animals to the
 human population
HEALTH-BASED EXPOSURE LIMITS
LOW-LEVEL EXPOSURE EVERY DAY

                ADI – Acceptable Daily Intake
The amount of a chemical which can be consumed every
day for a lifetime in the practical certainty, on the basis of
all known facts, that no harm will result
 Usually derived from lifetime dosage studies in animals

HIGH-LEVEL EXPOSURE ON OCCASIONAL DAYS

             ARfD – Acute Reference Dose
  Analogous to the ADI but relates to the amount of a
chemical that may be taken in at one meal or on one day
   Usually derived from short-term studies in animals
   Are pesticide residues safe?
  A beginner’s guide to risk assessment

1. What is risk assessment?
2. How does the PRC use risk assessment?
3. Does the PRC take account of the latest
   science?
4. Does the PRC consider combined intakes (the
   "cocktail effect")?
The building blocks for PRC risk assessment

ADI – acceptable daily intake
ARfD – acute reference dose
Median level found
Highest level found

Established by independent national and
international bodies such as
ACP – UK Advisory Committee on Pesticides
JMPR – WHO-FAO Joint Meeting on Pesticide Residues
PPR Panel – Plant-protection Products and their
Residues Panel of EFSA
The building blocks for PRC risk assessment

ADI – acceptable daily intake
ARfD – acute reference dose
Median level found
Highest level found

Derived from the individual pesticide residue
survey and combined with food intake data from
the most recent national UK survey
Interpretation of pesticide residue data

RISK CHARACTERISATION
LOW-LEVEL EXPOSURE EVERY DAY
Compares the average daily intake with the ADI

The average daily intake is calculated using the median
residue level found and the long-term average intake of
that food commodity for “high-consumers” (97.5th
percentile of range) in 10 different consumer groups
Interpretation of pesticide residue data

RISK CHARACTERISATION
HIGH-LEVEL EXPOSURE ON OCCASIONAL DAYS
Compares the occasional high intake with the ARfD

The occasional high intake is calculated using the
highest residue level found (with correction for
possible non-uniform distribution within crop) and the
intake of that food commodity on a single day for
“high-consumers” (97.5th percentile of range) in 10
different consumer groups
Where does the MRL fit in?
        HAZARD            GOOD AGRICULTURAL
     IDENTIFICATION            PRACTICE




       HAZARD              MAXIMUM RESIDUE
   CHARACTERISATON          LEVELS (MRLs)

   ESTABLISHMENT OF
    A HEALTH-BASED
     EXPOSURE LIMIT
    e.g. an ADI or ARfD

WHEN ARE THE ADI/ArfD AND THE MRL
   BROUGHT TOGETHER IN RISK
      CHARACTERISATION ?
       HAZARD            GOOD AGRICULTURAL
    IDENTIFICATION            PRACTICE




      HAZARD              MAXIMUM RESIDUE
  CHARACTERISATON          LEVELS (MRLs)

  ESTABLISHMENT OF
   A HEALTH-BASED
    EXPOSURE LIMIT
   e.g. an ADI or ARfD

 The MRL would only be accepted if the
resulting intakes are below the ADI/ARfD
         HAZARD            GOOD AGRICULTURAL
      IDENTIFICATION            PRACTICE




        HAZARD              MAXIMUM RESIDUE
    CHARACTERISATON          LEVELS (MRLs)

    ESTABLISHMENT OF
     A HEALTH-BASED
      EXPOSURE LIMIT
     e.g. an ADI or ARfD

BUT intakes due to residues at the MRL may
 be considerably lower than the ADI/ARfD
         HAZARD            GOOD AGRICULTURAL
      IDENTIFICATION            PRACTICE




        HAZARD              MAXIMUM RESIDUE
    CHARACTERISATON          LEVELS (MRLs)

    ESTABLISHMENT OF
     A HEALTH-BASED
      EXPOSURE LIMIT
     e.g. an ADI or ARfD

  Therefore residues above the MRL do not
always result in intakes above the ADI/ARfD
   Are pesticide residues safe?
  A beginner’s guide to risk assessment

1. What is risk assessment?
2. How does the PRC use risk assessment?
3. Does the PRC take account of the latest
   science?
4. Does the PRC consider combined intakes (the
   "cocktail effect")?
The building blocks for PRC risk assessment

ADI – acceptable daily intake
ARfD – acute reference dose
Median level found
Highest level found

The ACP, JMPR and EFSA-PPR Panel are
responsible for the continued monitoring of
scientific developments and for making changes
to the ADI/ARfD.
PRC uses the most recent values and undertakes
additional risk assessments when appropriate.
   Are pesticide residues safe?
  A beginner’s guide to risk assessment

1. What is risk assessment?
2. How does the PRC use risk assessment?
3. Does the PRC take account of the latest
   science?
4. Does the PRC consider combined intakes (the
   "cocktail effect")?
Ingestion of a mixture of residues may occur:-

1. when a single food product contains more
   than one pesticide or
2. when different foods in a meal contain
   different residues
Interactions between pesticides can be of 2 types

1. Dose addition
Mixtures where the different compounds produce
the same adverse effect(s) at high doses
For such mixtures the total effect is predicted by
adding the different doses (after allowing for
differences in potency) – dose addition.
In such as cases it is possible for combinations of
lots of low and inactive doses could produce an
effect – relevant to low level multi-residue
exposures
Mixtures of pesticides can be divided into 2 types

2. Response addition
Mixtures where the different compounds produce
different adverse effect(s) at high doses
For such mixtures each component will express
its own effect independently of the presence of
other compounds – response addition.
In such as cases combinations of lots of low and
inactive doses will NOT produce an effect – not
relevant to low level multi-residue exposures
Risk assessment when a single food
product contains more than one pesticide

OPs and carbamates produce the same effect at
high doses.

PRC calculates the 97.5th percentile intake for
each compound detected in the single food as a
percentage of its ARfD and sums the different
percentages – Dose Addition
Risk assessment when different foods in a
meal contain different residues
It is unrealistic to assume that the same person
will be the 97.5th percentile consumer for each
different food found to have a residue.

Analysis of this issue requires a sophisticated
probabilistic approach and suitable methods and
databases are still under development
CONCLUSIONS
There are well established procedures for the approval of
pesticides by the WHO, the EC and the UK
The ADI and ARfD are based on comprehensive databases
using internationally agreed methods; safety factors allow for
species differences and human variability
MRLs are derived from supervised field trials and the potential
exposures compared with the ADI and ARfD
Results from the residue surveillance programme undergo a
risk assessment using internationally accepted methods
Recent developments are incorporated into the ADI/ARfD
when the findings are valid and accepted internationally
Multiple exposures are considered for data in each survey
Additional slides for discussion
Safety is not an absolute term

        Benefit                                     Benefit




         Safe                                      Pesticide
                                                   residues
Risk                    Cost          Risk                              Cost


A comprehensive risk-cost-benefit analysis is
necessary for a rational discussion of the “safety”
of pesticide residues in food
                  From D.Williams What is safe? The Risk of Living in a Nuclear Age
Current International Activities on Mixtures

2007- EFSA Colloquium on Pesticide Mixtures (which will
       become a PPR-Panel Opinion)
2007- IPCS meeting on aggregate and cumulative
       exposures to chemicals
2007- IGHRC proposal on risk assessment of mixtures to
       be reported and available for comment
2007- HESI and ECETOC also have projects in this area

								
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