The purpose of the dietary risk assessment is to assess risks to human health resulting from pesticide residues on, or in, food. Pesticide residues in food may result from application of pesticides to edible crops ie directly or indirectly through rotational crops or the use of treated crops or by-products of crops as animal feed. Pesticide residues include the residues of active substance and the residues of (toxicologically) relevant degradation products (metabolites) that remain on or in food or feed.
A key component of the dietary risk assessment is the establishment of toxicological reference values for acute and chronic exposure, respectively. Assessment factors are used in setting the reference values.
Dietary risks of the expected residues following long-term and short-term exposure are considered. The risk to human health is considered acceptable when estimated long-term and short-term dietary intake of pesticide residues do not exceed the relevant toxicological reference value.
Assessments are carried out for each crop or crop group that is included on the label. The use pattern that will result in the highest potential for residues (for example the highest proposed rate, most frequent applications and shortest withholding period) is used as the basis of the assessment. Maximum residue limits/tolerances for the pesticide for each commodity are set provided the dietary exposure calculation confirm that the levels to no pose a risk to human health.
The Codex Alimentarius Commission (Codex) is an international food standards setting body. The Codex Committee for Pesticide Residues is responsible for establishing Codex maximum residue limits for pesticides in food or feed that move in international trade. The maximum residue limits set by Codex may differ to those set by individual countries or regions, due to factors such as different dietary patterns, environmental conditions and national practices.
What this page contains
This table summarises the principles applied during the risk assessment to determine whether the human health risk criteria in relation to dietary risks are acceptable.
Summary analysis
While there has been much effort and success in harmonising test guidelines and assessment methods for the evaluation of dietary risks the reader must be aware that a key factor of whether the human health risks in relation to dietary risks are acceptable in a particular country or region is the local use pattern and the local population food consumption data.
The Codex Alimentarius Commission (Codex) develops international standards relating to the maximum residue limits of pesticides in food or feed for the purposes of international trade. The Codex maximum residue limits can differ from those set by individual countries or regions due to different local agricultural practices.
The area of dietary risk assessment is complex as it may take into consideration exposure sources other than food, for example drinking water and require special consideration of risks to infants and children in some countries such as the US.
Aspect | Description |
Links to risk assessment guidelines, manuals and science policy documents | |
Hazard assessment and end-point selection | - The output of the hazard assessment is the identification of the NOAEL
- The toxicological studies are re-viewed to assess the most suitable NOAEL from long-term (chronic) animal studies
- The toxicological studies are re-viewed to assess whether there are any demonstrable toxicological effects from a single dose
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Setting of toxicological reference values and the use of assessment factors | Toxicological reference values for acute and chronic exposure scenarios are determined by: - applying a 100-fold uncertainty factor (or higher if necessary) to the most suitable NOAEL from long-term (chronic) animal studies to establish an ADI value
- applying a 100-fold safety factor (or higher if necessary) to the most suitable NOAEL from single (day) expo-sure to establish an ARfD
- The 100-fold safety factor is based on a 10-fold uncertainty factor for interspecies variation and a second 10-fold factor for intra-species variation. A higher safety factor may be applied depending on the completeness of the toxicological database.
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Residue evaluation and the setting of maximum residue limits | Establishing a residue definition
July 2014: https://apvma.gov.au/node/1019
- a residue is defined as the chemical, its metabolites and related components to which the MRL applies
- the inclusion of specific metabolites or degradation products in the expression of the residue depends on their toxicological profile and the extent to which they occur
- metabolites that occur at levels greater than 0.1mg/kg or that comprise more than 10% of the total radioactive residue should be identified.
- analytical methods must be available to determine the residue levels in a range of substrates
Residue analytical methods
July 2014: https://apvma.gov.au/node/1031
Residue analytical methods should: - have the ability to determine (identify, quantify and confirm) all the components included in the residue definition
- be specific enough that interfering substances never exceed 30% of the limit of analytical quantitation
- have demonstrated repeatability
- cover all crops and animals that may be treated
- cover animal and crop products if residues above the limit of analytical quantitation may occur
- cover all edible animal products if animals are likely to consume treated crops
- when possible, identify which multi-residue methods have the capacity to measure the residues
Residue trials to obtain permanent maximum residue limits for crops (Residues), July 2014: https://apvma.gov.au/node/1028
Residues (Part 5A)
June 2016
https://apvma.gov.au/node/1037
- The general expectation is that residue trials have been conducted in Australia. The datasets should be spread across representative cropping areas or geographic locations in Australia and may also include trials conducted din other countries, if the use pattern and GAP in those countries are considered to be similar to Australia’s.
- The results relevant to the use pattern are considered and appropriate MRLs are determined. The OECD MRL calculator may be used to estimate the MRL
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Exposure assessment - dietary risk assessment | - The risk assessment for long-term (chronic) and short-term (acute) dietary exposure is based on the expected residue, the toxicological reference values (called the health based guidance values) for the active constituent and Australian consumption figures for the relevant food commodities
- The dietary exposure calculations are based on international methodologies using Australian consumption data derived from national nutritional surveys
- Food Standards Australia and New Zealand play a key role in the dietary exposure assessment
http://www.foodstandards.gov.au/science/exposure/Pages/dietaryexposureandin4438.aspx
Chronic dietary exposure assessment - The chronic dietary exposure to the active is estimated by the NEDI calculation encompassing all registered uses of the active and the mean daily dietary consumption data. The NEDI calculation is made in accordance with WHO Guidelines IEDI
Acute dietary exposure assessment - The acute dietary exposure assessment is estimate by the NESTI calculation. The NESTI calculations are made in accordance with the deterministic method used by the JMPR IEST.
- A separate calculation is conducted for children (2-6 years of age) and the general population (2+ years). If an ARfD is only set for women of childbearing age then one calculation for that cohort only is conducted.
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Risk assessment and acceptability criteria | The safety criteria are met if the risk assessment establishes that both chronic and acute dietary exposure is considered acceptable and appropriate MRLs have been set.
- Chronic dietary exposure is considered acceptable where the NEDI calculates as less than 100% of the ADI.
- Acute dietary exposure is considered acceptable where the NSTI calculates as less than 100% of the
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Aspect | Description |
Links to risk assessment guidelines, manuals and science policy documents | |
Hazard assessment and end-point selection | - A NOAEL is selected for a toxic end point observed in animals that is relevant to humans, and it is usually from a study in which animal exposure is representative of the route, frequency and duration of human exposure.
- An appropriate NOAEL from chronic animal toxicity studies is identified
- An appropriate NOAEL from acute animal toxicity studies is identified
- Cancer end points are identified as a cancer potency factor if the effects are a linear response or a Point of Departure (eg NOAEL) if the effects are a non-linear response.
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Setting of toxicological reference values and the use of assessment factors | - The ADI is calculated using the appropriate NOAEL from chronic animal toxicity studies and applying the appropriate uncertainty factors.
- The ADI the PMRA generates is equivalent to the chronic Populated Adjusted Dose (cPAD) that is generated by the US EPA.
- The ARfD is calculated using the appropriate NOAEL from acute animal toxicity studies and applying the appropriate uncertainty factors.
- The ARfD that the PMRA generates is equivalent to the acute Population Adjusted Dose (aPaD) that is generated by the US EPA.
- Uncertainty factors are based a 10-fold factor to account for inter-species variation and an additional 10-fold factor to account for intra-species variation. In certain cases, up to an additional 10-fold safety factors may also be applied for sensitive subpopulations, or for the protection of children and offspring, depending on the severity of the toxicological endpoints, or for concerns or uncertainties about the precision of toxicity and exposure estimates.
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Residue evaluation and the setting of maximum residue limits | In establishing a residue definition Canada follows OECD test guidelines and guidance This guidance document provides a common approach to residue identification of the pesticide and its metabolites and degradation products - a pesticide residue is the combination of the pesticide and its metabolites, degradates and the transformation products
- the residue for dietary risk assessment focuses on the parent compound and toxicologically significant metabolites taking into consideration exposure and toxicity
- the residue for MRL enforcement purposes focuses on those analytes which would indicate a possible misuse of the pesticide and can be practically detected by a broad base of laboratories
For residue analytical methods Canada follows OECD test guidelines and guidance The guidance document provides guidance on residue analytical methods used to generate data for estimating dietary exposure assessments, to establish MRLs and to determine processing factors. Analytical methods are also used in enforcement of MRLs. Methods should: - include all the analytes in accordance with the residue definition
- be sufficiently selective so the interfering substances never exceed 30% of the limit of analytical quantitation
- demonstrate acceptable recovery and repeatability
- cover all corps, animals and feed items being treated
Residue study requirements and MRL calculation
The number of trials and how they should be distributed across geographic and climatic regions are set out at: Crop trial requirements for trials conducted to support simultaneous domestic registration applications in both Canada and the United States are detailed in:
Science Policy Note: Guidelines for Reduced Residue Field Trial Requirements to Support Joint Projects between Canada and the United States, July 2017
Canada uses the OECD MRL Calculator to calculate MRLs |
Exposure assessment - dietary risk assessment | - Aggregate exposure from exposures from all food residues and drinking water is considered.
- Estimates of exposure from food are derived from the amount of pesticide residue that is present in or on food (residue level) and the types and amounts of food that people eat (food consumption)
- Consumption data comes from the National Health and nutritional Examination Survey, What We Eat in America (NHANES/WWEIA) which provides survey data of what people eat in the US and Canada
- Dietary risk (from acute or chronic exposure) is calculated using a model that combines food exposure data (residue levels and percent of the crop treated, and consumption) and toxicity to product a risk value. The model is called the Dietary Exposure Evaluation Model (DEEM).
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Risk assessment and acceptability criteria | - Chronic food risk is expressed as a percentage of the ADI. If the calculated %ADI is less than 100, the risk is generally considered to be acceptable.
- Acute food risk is expressed as a percentage of the ARfD. If the calculated %ARfD is less than 100, the risk is generally considered to be acceptable.
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Topic | name |
Links to risk assessment guidelines, manuals and science policy documents | |
Hazard assessment and end-point selection | Toxicology data of the pesticide should be comprehensively reviewed and evaluated to fully obtain its toxicity information. Special attention should be paid to the presence of mutagenicity, reproductive and developmental toxicity, carcinogenicity, neurotoxicity and other special toxic effects in the process of toxicity evaluation.
Generally, data from chronic toxicity, reproductive and developmental toxicity, carcinogenicity studies can be used to establish NOAEL. |
Setting of toxicological reference values and the use of assessment factors | NOAEL divided by an appropriate uncertainty factor equals ADI.
The uncertainty factor is typically 100, which is the coefficient used to extrapolate data from experimental animal to the general population (interspecies differences), and from the general population to sensitive populations (intra-species differences). The coefficients for interspecies and intra-species differences are both 10.
In addition to interspecies and intra-species differences, other considerations when selecting an uncertainty factor include the quality, reliability and completeness of the toxicity data, the nature of the adverse effects, and the degree of matching between test conditions and actual scenarios. Based on each individual case and relevant data, the uncertainty factor can be appropriately amplified or reduced accordingly. Although there are multiple sources of uncertainty, the uncertainty factor should not exceed 10,000 even with significantly inadequate data. |
Residue evaluation and the setting of maximum residue limits | The residue definition includes the active ingredient, and its metabolites, degradation products, which are of toxicological concern.
Most of residue definition refer to Codex definition.
Residue analytical methods
For detailed information refer to the Guidelines for the Compilation of National Standards for Pesticide Residue Analytical Methods
Residue studies for setting tolerances
Test Guideline on Residues Field Trials (NY/T 788-2018)
All residue data arising from supervised field trails, which reflect the recommended use pattern, such as application dosage, duration, frequency and interval of application, PHI
The number and distribution of residue field trails should refer to Data Requirement on Pesticide Registration and Guidance on the Distribution of Residue Field Trails
Sampling methods should refer to NY/T 788-2018 |
Exposure assessment - dietary risk assessment | Dietary intake assessment is an estimate of pesticide dietary intake, both long-term and short-term, based on toxicological and residual chemical assessments, and dietary consumption of Chinese residents.
National estimated daily intakes (NEDIs) is calculated for Long-term dietary intakes assessment.
NEDI =∑［STMRi（STMR-Pi）× Fi）］
F refers to consumption data, and comes from the Report on Monitoring the nutrition and health status of Chinese residents.
For further information refer the Guidelines for Pesticide Residue Risk Assessment in Foo. |
Risk assessment and acceptability criteria | When estimated NEDI or NESTI does not exceed the ADI or the ARfD, the proposed MRL based on GAP is unlikely to present a public health concern.
For further information refer to the Guidelines for Pesticide Residue Risk Assessment in Food. |
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Aspect | Description |
Links to risk assessment guidelines, manuals and science policy documents | |
Hazard assessment and end-point selection | - Reference points for chronic exposure are derived from results of long-term animal toxicity studies (normally the NOAEL)
- The toxicological studies are reviewed to assess whether there are any demonstrable toxicological effects from a single dose
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Setting of toxicological reference values and the use of assessment factors | - An uncertainty factor of 100 (or higher, if necessary) is applied to convert the relevant end point into the ADI.
- A 100-fold safety factor is applied to the most suitable NOAEL from single (day) exposure to establish an ARfD
- The Benchmark Dose approach may be used as an alternative way of defining reference points for a risk assessment.
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Residue evaluation and the setting of maximum residue limits | - residues are defined as the substances (including their metabolites, breakdown or reaction products ) present in or one plants or plant products, edible animal products, drinking water or elsewhere in the environment resulting from the use of the pesticide
- the residue definition should consider all compounds of toxicological significance, taking into account the amounts likely to be present in food or feed
- further assessment is performed for metabolise contributing both >= of the total radioactive residue and >= 0.01mg/kg in plant food and feed commodities or >= 0.05 mg/kg independent of the percent total radioactive residue in food commodities
Residue analytical methods should: - be appropriate to the residue definition
- include analytical calibration of sufficient range for determination of recoveries and for assessment of the level interference
- include data to support recovery and precision/repeatability are required
- use multi-residue methods published by an international official standardisation bodies are acceptable
Residue trials and MRL calculations |
Exposure assessment - dietary risk assessment | - Chronic (long-term) and acute (short-term) dietary consumer exposure to pesticide residues are estimated using a calculation model (PRIMo - Pesticide Residue Intake Model). The model is based on national food consumption data and units weights provided by Member States and implements internationally agreed risk assessment methodologies.
Pesticide evaluation; Tools Calculator-Tools
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Risk assessment and acceptability criteria | The decision-making criteria specify that, taking into account all registered uses, the proposed use shall not be authorised if the best possible estimate of dietary exposure exceed the ADI |
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Aspect | Description |
Links to risk assessment guidelines, manuals and science policy documents | |
Hazard assessment and end-point selection | - A margin of safety approach is used for toxic end points that have threshold effects. A NOAEL is selected for a toxic end point observed in animals that is relevant to humans and it is usually from a study in which animal exposure is representative of the route, frequency and duration of human exposure.
- For acute (non-cancer) toxicological effects a NOAEL is selected from acute animal toxicity studies
- For chronic (non-cancer) toxicological effects a NOAEL is selected from chronic animal toxicity studies
- A quantitative risk assessment approach is used for for non-threshold effects such as cancer. Data from laboratory and animal studies together with mode of action studies are used to decide if a pesticide is likely to pose a cancer risk. Statistical models are used to estimate potential cancer risk in humans.
Cancer end points are identified as a cancer potency factor if the effects are a linear response or a Point of Departure (eg NOAEL) if the effects are a non-linear response. - When sufficient data are available a benchmark dose approach involving dose-response modelling may be used to better define dose/response levels at the low end of the observable range of data
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Setting of toxicological reference values and the use of assessment factors | A reference dose is calculated by dividing the NOAEL by uncertainty factors.
A 10-fold uncertainty factors is applied to account for inter-species variation and further 10-fold factor is applied to account for intra-species variation. Additional uncertainty factors ranging in magnitude of 3-fold to 10-fold may be applied to account for gaps in the toxicity database and/or if a LOAEL is used instead of a NOAEL.
The law specifically requires that an additional 10-fold safety factor is applied to assure the safety of infants and children unless there is data to demonstrate that a different safety factor should apply. The reference value is converted to an aPAD and an cPAD (for acute and chronic exposure, respectively) by dividing the reference dose by the safety factor.
Further information on how appropriate safety factors are determined can be found at https://www.epa.gov/sites/production/files/2015-07/documents/determ.pdf
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Residue evaluation and the setting of maximum residue limits | Establishing a residue definition
Residue Chemistry Test Guideline OPPTS 860.1300
Nature of the Residue - Plants, Livestock
- the sum of the parent pesticide and its degradation products, metabolites and impurities which are of toxicological concern are defined as the total toxic residue
- analytical methods must be developed for all components of the total toxic residue
Residue Chemistry Test Guideline OPPTS 860.1340
Residue Analytical Method
Residue analytical methods are required for all components of the total toxic residue and:
- must allow identify and magnitude of residues from proposed to be determined
- must provide a means for enforcement of the tolerance
- should not be subject to substrate-related interferences or those arising from reagents
- use of multi residue methods for enforcement purposes are encouraged
Residue studies for setting tolerances
Residue Chemistry Test Guideline OPPTS 860.1500
Crop Field Trials
Crop field trails should reflect the pesticide use patterns the could lead to the highest possible residue - data are required for each crop of representatives crops for each crops group for which tolerances are to be set
- the number of trials and how they should be distributed across geographic and climatic regions are set out in the test guideline document
The US uses the OECD MRL Calculator to calculate pesticide tolerances |
Exposure assessment - dietary risk assessment | - Aggregate exposure from exposures from all food residues and drinking water is considered.
- Estimates of exposure from food are derived from the amount of pesticide residue that is present in or on food (residue level) and the types and amounts of food that people eat (food consumption)
- Consumption data comes from the US DA’s CSFII which provides survey data of what people eat in the US
- Dietary risk (from acute or chronic exposure) is calculated using a model that combines food exposure data (residue levels and percent of the crop treated, and consumption) and toxicity to product a risk value. The model is called the Dietary Exposure Evaluation
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Risk assessment and acceptability criteria | - Chronic food risk is expressed as a percentage of the cPAD. If the calculated %cPAD is less than 100, the risk is generally considered to be acceptable.
- Acute food risk is expressed as a percentage of the aPAD. If the calculated %aPAD is less than 100, the risk is generally considered to be acceptable.
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Aspect | Description |
Links to risk assessment guidelines, manuals and science policy documents | |
Hazard assessment and end-point selection | - The output of the hazard assessment is the identification of the NOAEL
- The toxicological studies are reviewed to identify the the most relevant NOAEL from long-term (chronic) animal studies
- The toxicological studies are reviewed to identify the NOAEL most relevant for a single (day) exposure
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Setting of toxicological reference values and the use of assessment factors | - The ADI and ARfD (if required) are derived from the NOAEL by application of an appropriate safety factor
- When using data obtained from experimental animals the default safety factor is 100 - comprising a factor of 10 to allow for inter-species differences and a factor of 10 for intra-species differences
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Residue evaluation and the setting of maximum residue limits | - A pesticide residue is the combination of the pesticide and its metabolites, degradates and other transformation products
- the residue definition should be
- based on a single compound whenever possible
- most suitable for monitoring compliance with GAP
- the same for all commodities if possible
- common moiety residues for MRL purposes should be avoided
- the residue definition for dietary risk assessment should include compounds of toxicological significance
Residue analytical methods should: - have the ability to determine all of the likely analytes that may be included in the residue definition (both for dietary risk assessments and enforcement) in the presence of the sample matrix
- distinguish between individual isomers/analogues when necessary for the conduct of dietary risk assessment
- be sufficiently selective so that interfering substances never exceed 30% of the limit of analytical quantification
- demonstrate acceptable recovery and repeatability
- cover all crops, including those used as feed, animal tissues, milk and eggs as appropriated and by-products used as feed
- cover all edible animal commodities if animals are likely to consume grated crops
- include processing fraction if detectable residues occur
- All residue data arising from supervised rials supporting or reflecting the reported GAP are examined
- Adequate number of independent trials are required reflecting the highest of national maximum GAPs and conducted according to well-designed protocols that consider geographical distribution and the inclusion of a number of different growing and management practices and growing seasons
- the maximum residue levels are primarily estimated based on the GAP that leads to the highest residue
- Statistically based methods to estimate MRLs such as the OECD MRL calculator may be used
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Exposure assessment - dietary risk assessment | To assess whether the MRL provides sufficient consumer safety, available residue data are combined with cultural dietary information to estimate potential residue intake by consumers.
The IEDI is calculated by multiplying the residue concentrations by the ‘average’ daily per capita consumption estimated for each commodity on the basis of the GEMS/Food diets and summing the intakes for each food.
The IESTI is calculated for the general population and for children less than 6 yours old using the GEMS/Food values for the highest large-portion diet.
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Risk assessment and acceptability criteria | The consumer is considered to be adequately protected when estimated dietary intake of pesticide residues does not exceed the ADI or the ARfD. |
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Considerable work has been done internationally to harmonise approaches in dietary risk assessments. The principles and policies followed in the hazard assessment and end-point selection for dietary risks and the setting of toxicological reference values are similar across regulatory frameworks. The principles and policies followed for a residue evaluation and the setting of maximum residue limits are also similar across regulatory frameworks. These components of the dietary risk assessment can be applied in any country.
The use of assessment factors is similar across regulatory frameworks but the output may vary depending on individual countries view on the completeness of the toxicological database and other factors such as sensitive subpopulations (including infants and children) and/or concerns and uncertainties about the data. The application of assessment factors in setting toxicological reference values needs to be considered on a case-by-case basis and align with the legislative requirements (where they are specified) and the data available.
While the acceptability criteria for a dietary risk assessment are similar across regulatory frameworks, the dietary risk assessment itself is based on local dietary consumption data. Dietary risk assessment models used by regulatory authorities are therefore based on local consumption data. As such the dietary risk assessment from one country/region cannot be readily applied to another country.
Codex MRLs are intended primarily to support the human health safety and compliance of food and feed commodities moving in international trade. The Joint Meeting on Pesticide Residues (JMPR) undertakes the dietary risk assessment that underpins the Codex MRLs. Important considerations when contemplating the application of the JMPR dietary risk assessment and outcomes such as the MRL are whether the active ingredient and produce specifications, the use pattern and agricultural practices, crop production and food consumption data on which those assessments and outcomes are based are similar in the adopting country. Advice on the use of JMPR recommendations by regulatory authorities is provided at http://www.fao.org/3/a-i5452e.pdf.
