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Risk Assessment of

Pesticide Residues
based on SPRT data

Sri Noegrohati
Fac of Pharmacy
Gadjah Mada University

Sri Noegrohati, GMU

Estimation of Pesticide
MRLs
Plant
metabolism

identity
of the
residue

Farm animal
metabolism

Lab animal metabolism studies

Establish the pesticide use pattern


necessary for pest control

Pesticide toxicology studies

Supervised field trials - measure


residues resulting from use pattern

Estimate values for


ADI and acute RfD

RISK ASSESSMENT
Are the toxicology and dietary
intake of residues compatible?

Set official MRL


Register use pattern on official label

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Hazard

The hazard is represented by the toxicological endpoint


(mg/kg body weight/day).
Select the most appropriate toxicological endpoint in
the most relevant species.
Select a toxicology study appropriate for duration of
the exposure.
Apply safety/uncertainty factors to establish reference
doses for use in risk assessments.

Dietary risk assessment

RISK = f(HAZARD, EXPOSURE)


EXPOSURE = f(CONSUMPTION, RESIDUE)

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HAZARD
CHARACTERIZATION

For chemical agents, a dose-response assessment


should be performed.
The qualitative and/or quantitative evaluation of the
nature of the adverse effects associated with biological,
chemical, and physical agents which may be present in
food.
Need appropriate data for the exposure scenario
High daily consumption for acute assessments
Average daily consumption for chronic assessments

Sri Noegrohati, G

Dose-response
extrapolation

Pesticide residues in food are at low levels - typically at


a part per million or less.
In order to be compared to human exposure levels,
animal data need to be extrapolated to doses much
lower than those studied.
The selected dose-response model may be incorrect
even if the nature of the response in animals and
humans is qualitatively the same.

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Dose response relationship


Human risk Assessment
Taxonomic diversity
One species

Toxicological endpoint
Effect, toxic and
Lethality
acute: ED50, TD50, LD50
Chronic: NOAEL

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Environmental risk Assessment

Millions species (10 to 100)


Focused on population and ecosystem level

Ecological function, reproduction


and growth, enzyme activity,
morphological structure, behavior
Complicated due to metamorphosis
Ecosystem can tolerate some stress
and occasional adverse effect a
small fraction of the taxa could be
unprotected 5% HC5

Repeated Toxicity testing

Repeated exposure (daily) for shorter or longer periods of time


may not produce immediate effect, but may
induce delayed effect due to accumulation of the chemical in
the body
Or other mechanism

More common for human exposure

The study is carried out with young animals in their growth


status, which is considered sensitive to exogenous agent

Standard method
OECD guideline 407 (14 to 28 days)
OECD guideline 408 (90 days) for subchronic studies

Provide an estimate of NOAEL

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No Observed Effect Level


(NOAEL)

The highest concentration or dose of a substance, determined by


experiment of observation, which causes no detectable adverse
alteration in morphology, functional capacity, growth development or life
span of the target organisms
Sri Noegrohati, G

Environmental Safety
evaluation

Based on Dose-response or exposure-effect relationship

Ecotoxicological safety evaluation: based on multi species


studies
Exposure: model of ecosystem to simulate real ecosystem,
closed or open system to the air, rainfall may be simulated
Multi species tests organisms, i.e. for terrestrial
ecosystem: representatif bacteria, plants and
invertebrates, at least 5 species of different taxa
Toxicological end point: NOAEL or NOEC

Criterion: Hazardous concentration for p% of species (HCP) =


probability of p% species from a community is affected

Usually HC5 exposure level which affect only 5% of the


community due to exceeding their NOAEL

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Scope

Organisms

Toxicity

End point

Test with plants


over several
generations in
freshwater
medium

Selenastrum
capricornutum
(microalgae).

Short term chronic


toxicity (72 h) of
dissolved
chemicals to
growing population

decreased growth rate


and lowered
reproductive capacity
IC50 by % growth
inhibition,

Test with plants at


early life stage in
freshwater
medium

Lepidium sativum,
Form:
Untreated seeds,
stored at 4C

Short term chronic


toxicity (5 days) of
dissolved
chemicals at early
life stage

Inhibition of seed
germination EC50
and %root elongation
IC50

Test with animal


in freshwater
medium

Daphnia magna, a
primary consumer
crustacean

Screening, Acute
toxicity (24h to 48h)
of dissolved
chemicals at early
life stage

ead neonates (not


moving for 15 sec.)
LC50 by % mortality

Test with animals


in estuarine and
marine waters
medium

Artemia francisana,
a thrive euryhaline
marine species,
Form: Cysts

Screening, Acute
toxicity (24h) of
dissolved
chemicals at the
early life stage

ead larvae (not


moving for 10 sec.)
LC50 by % mortality

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CONSUMPTION

Food Balance sheets on a country-level, (WHO-GEMS)


Product
Rice
Wheat
Potatoes
Soya sauce
Sugar refined
TOTAL OF VEGETABLE
OILS AND FATS
Brassica vegetables
Cabbages
Fruiting veg. Cucurbits
Fruiting veg. Noncucurbits

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Far Eastern
Consumption
g/person/day
279.30
114.80
19.20
11.00
43.00
14.20
11.20
9.70
18.20
12.50
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Intake g/person/day

Food Intake

WHOGEMS

BPS
(2005)

TOTAL CEREALS

617.0

282.7

TOTAL ROOTS AND TUBERS

119.7

40.3

TOTAL PULSES

41.9

17.5

TOTAL SUGARS AND HONEY

58.6

TOTAL NUTS AND OILSEEDS

42.6

14.9

TOTAL VEGETABLE OILS AND


FATS

14.9

12.2

TOTAL STIMULANTS

2.9

TOTAL SPICES

2.3

TOTAL VEGETABLES

270.9

106.0

TOTAL FISH AND SEAFOOD

47.4

40.8

TOTAL EGGS

22.1

17.5

148.4

67.9

66.0

7.1

TOTAL FRUITS
TOTAL MILK AND MILK
PRODUCTS
Sri Noegrohati,
G
TOTAL MEAT
AND OFFALS

77.6

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14.9

Probabilistic Dietary Risk Assessment


Number of samples

Exposure = f(consumption distribution, residue distribution)


x variability and
processing factors

Distribution of exposure

Compare to
tox endpoint

Number of People

Number of People

Distribution of residues

99.9th percentile

Distribution of consumption

Exposure (mg/kg bw/d)

Amount Food Consumed (kg/person/day)

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Risk Assessment of long-term (chronic)


exposures to pesticide residues in food

INPUTS
Acceptable Daily Intake (ADI)
estimate of the amount of a substance in food
and/or drinking-water, normally expressed on a
body weight basis, that can be ingested daily over
a long-term (month, year, lifetime), without
appreciable health risk to the consumer on the
basis of all the known facts at the time of the
evaluation.
ADI are expressed in mg substance/kg body
weight/day.

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Risk Assessment of long-term (Cont)

INPUTS

Consumption: Average daily Diets based on food


balance sheets
For

chronic dietary intake the median represents


the long term typical residue if a consumers diet is
consistently derived from crops treated at
maximum GAP (highest registered application rate,
minimum pre-harvest interval, etc).
The STMR is a good starting point for chronic
intake estimation (SPRT).

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Calculation of Chronic
Intake
TMDI = (MRLi Fi)
IEDI = (STMR-Pi Fi)
Where:
MRLi

MRL for food commodity i

STMRi (or
STMR-Pi)

STMR (or STMR-P) for food commodity i

Fi

GEMS/Food regional consumption of food


commodity i

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Risk Assessment of short-term


(acute) exposures to pesticide
residues in food

Acute Reference Dose


The acute RfD of a chemical is an estimate of the
amount of a substance in food and/or drinking-water,
normally expressed on a body weight basis, that can
be ingested over in a period of 24 hours or less,
without appreciable health risk to the consumer on the
basis of all the known facts at the time of the
evaluation (JMPR 2002)
Residue Trials data (SPRT)
Supervised residue trials: HR

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Calculation of Acute
Intake

International Estimate of Short-Term Intake (IESTI)


Case 1
Composite sample reflects residue level in a daily
Large Portion (LP) of the food.

IESTI =

LP * HR
bw

Large portion size - 97.5th percentile of eaters of


that food.
Children and total population

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Risk Evaluation
Example: SPRT of Deltamethrin in Indonesia

Long term risk assessment


National Estimated Daily intake, NEDI, 18.9
g/person or 3% ADI,
International Estimated Daily intake, IEDI, highest
calculated was 147.1 g/ person or 20% ADI.

Short term risk assessment

National Estimated Short Term Intake, NESTI average


adult 0.004 g/kg b.w. or.008% ArfD,
International Estimated Short Term Intake, IESTI,
calculated based on US uptake 0.038 g/kg bb.
or.026% ArfD.

STMR obtained from SPRT of Deltamethrin in Indonesia


could be used as proposed MRLs
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Recommendation for Deltamethrin


MRL

Deltametrin residue data from SPRT carried out in


Indonesia: STMR 0.006 mg/kg,
95th percentile 0.0179 mg/kg
99.5th percentile 0.0358 mg/kg
Since the highest residue data observed was 0.014
mg/kg,
The recommended MRL for Deltamethrin
in fresh hot chilli pepper : 0.03 mg/kg

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Preparing a Data
Submission

Structure
Directory
1. Background information
2. Metabolism and environmental fate
3. Methods of residue analysis and data on freezer
storage stability
4. Use pattern
5. Residues resulting from supervised trials
6. Fate of residues in storage and processing
7. Residues in animal commodities
8. Residues in food in commerce or at consumption
9. National maximum residue limits and residue
definitions

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[LOGO]
TITLE:

[COMPOUND].
[NATIONAL GOVERNMENT]
SUBMISSION FOR JMPR 2005.

PURPOSE:

To provide information on [compound] to the FAO Secretary of


JMPR for evaluation by JMPR at the 2005 meeting.
[Compound] is on the FAO Panel schedule as a [periodic
review] compound for evaluation in 2005.

REPORT NUMBER:

[unique identifying number]

NUMBER OF PAGES:

[n] pages + annex + attachments

DATE OF ISSUE:

[xxxxx].

AUTHORS:

[Names of responsible authors and contact

Background information:
explain the reasons
for the data
submission and
briefly list the
information included
in the report

persons]
ADDRESS:
[Full address

]
AUTHORISATION:

[Head of national delegation to CCPR or other


relevant position]

ADDRESS:

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Analytical methods
Summary information for each method is provided.
Method identification number and reference:
Substrates: [e.g. plant material, vegetable oils, wine]
Analytes: [parent compound, metabolite 1, etc]
LOQ: [0.05 mg/kg]
Recoveries: [e.g. 78-110% for plant material spiked at 0.05 to 2 mg/kg, n=12]
Method description: [Very brief summary, for example: Homogenized sampl es were
extracted with aqueous methanol. The extract was cleaned-up on a cation
exchange cartridge. HPLC (single-column or two-column-switching systems) with
UV detection (max 270 nm) was used for the final measurement.]

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Use pattern

Summarise use patterns as provided on labels.


Ensure that the use pattern in the trials matches a label
use pattern

Table 1. Registered uses of [compound] in [country].


Crop
Apples

Formulation Method
WP 900

foliar

Cherries SC 400

foliar

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Timing

Rate kg ai/ha

Spray conc
ka ai/hl

from bud
opening
from petal
fall

0.90

0.090

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0.040

28

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No PHI,
days

Residue trials - supporting


information 1

Crop:
Study report identification number:
Analytical method ident number:
Procedural recoveries:
Trial design:
Plot size:
Sprayer:
Sprayer calibration:

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Residue trials - supporting


information 2

Field sample size:


Sampling dates:
Analysis dates:
Interval of sample storage:
Sample storage conditions:
Residue levels in samples from control plots:
Residues adjusted for % recovery?

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Summary of residue trials

Table 1. [Parent compound] and [metabolite M] residues in [commodity]resulting from


supervised trials in [country].
CROP
country, year
(variety)

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Application
Form

kg ai/hakg ai/hl

PHI
water,
l/ha

Residues

no. days Commodity [parent] [metab]


mg/kg mg/kg

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Ref

Residues in food in
commerce or at
consumption

Summarise residue monitoring data in standard tables.


In the residue monitoring data from the [national
government] residue survey, results of 2003-2004, [list of
commodities] were analysed for [compound] residues.

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