Clubes de convergencia para indicadores de

The current approach for dietary risk assessment as part of the pesticide registration process is deterministic and involves three steps:

1. Conduct supervised field trials to provide information on residue levels in and on RACs.

2. Deterministic intake assessment using the International Estimate of Short Term Intake (IESTI) equations. These are based on conservative consump- tion estimates and conservative residue levels obtained from supervised field trials.

3. Comparison of the intake assessment with an acceptable intake estimate lead- ing to acceptance or rejection of the pesticide use and the MRL.

We discuss each step in detail in the following sections and a summary of the process is shown in Figure 1.3. Supervised Field Trial MRL Proposal Median (STMR) & Highest Residue (HR) Consumption Data Conservative Consumption NEW USE Acute Intake Assessment (IESTI) IESTI ≤ ARfD? Modify use conditions? MRL / New Use Accepted Acute Reference Dose (ARfD) NO YES MRL = LOD NO YES

Figure 1.3 – Use of supervised field trial data for dietary risk assessment and MRL setting.

1.3.2.1 Residues from Supervised Field Trials

Supervised field trial data (see Section 1.3.1.1) are used to propose MRLs and to provide the Supervised Trials Median Residue (STMR) and Highest Residue (HR) for use in intake assessments (blue boxes in Figure 1.3).

1.3.2.2 Intake Assessment

Dietary risk assessment for pesticides focuses on effect levels and intake estimates in order to establish that pesticide usage is unlikely to lead to impacts on health when a high-residue unit is consumed or when someone consumes a treated product over a longer period. Intake estimation is based on two factors: residue levels on food items and consumption amounts of food items. Regulation EC 396/2005 (EC, 2005) states that the acute exposure of consumers to pesticide residues via food products should be evaluated taking into account the guidelines published by the World Health Organisation (WHO, 1997).

Intake assessments are based on the following simple equation:

Intake (mg/kg/day) = Amount Consumed (kg/day) × Concentration (mg/kg) Body weight (kg)

where consumption is divided by body weight to enable a comparison with the out- come of a toxicological effect assessment. The World Health Organisation (WHO) proposed the IESTI equations as a measure of acute dietary exposure (JMPR, 2002). To calculate the IESTI the following definitions are used:

LP Largest portion provided (kg food/day).

STMR Supervised trials median residue (mg/kg food).

STMRP Supervised trials median residue (mg/kg food) in processed

commodity, calculated by multiplying the STMR in the raw commodity by a processing factor.

HR Highest residue (mg/kg food) in composite sample of edible portion from the supervised field trials from which the proposed MRL and STMR were derived.

HRP Highest residue (mg/kg food) in the processed commodity, calculated by

multiplying the HR in the raw commodity by a processing factor.

bw Average consumer body weight (kg), from the country that provided the dietary survey with the selected largest portion, LP .

U Unit weight (kg) of edible portion, converted from the RAC provided by a country in the region where the supervised field trials were carried out that resulted in the highest residue level.

v The variability factor, v, is a measure used to reflect the variability of residue levels in or on individual commodity units and is defined as the 97.5th percentile of the distribution of unit residues divided by the mean residue level (EFSA, 2005). It is applied to account for the fact that some of the units making up the composite sample may have had higher

residue levels than the residue level of the composite sample itself.

For the deterministic IESTI calculations, the 97.5th _{percentile consumption value}

of a RAC is often used as the LP (JMPR, 2002). This means that 2.5% of the population is consuming a larger portion of the RAC than the LP . However, as the IESTI equations consist of some conservative estimates (e.g. HR) and residue levels from supervised field trials are assumed to be higher than residue levels in food items available on the market, it is unclear what level of protection is achieved. The IESTI is calculated using one of 3 standard equations, depending on the type of commodity involved (JMPR, 2002):

Case 1

This case is used for commodities for which a meal-sized portion consists of a number of units that is similar to the number of units in a composite sample (e.g. peanuts, grapes). The concentration of residue in a composite sample (raw or processed) reflects that in a meal-sized portion of the commodity (unit weight <25g).

IESTI = LP × (HR or HRP) bw

Case 2

This case reflects the situation where a consumer eats a few units (but less than the number in a composite sample) in one day, one of them possibly having high residue levels (e.g. apples). A meal-sized portion, such as a single piece of fruit or vegetable, might have a higher residue than the composite (unit weight of the whole portion is >25g). Standard variability factors, v, are applied in the equation unless sufficient data are available on residues in single units to calculate a more realistic variability factor.

IESTI =      U ×(HR or HRP)×v+(LP −U )×(HR or HRP) bw if U ≤ LP U ×(HR or HRP)×v bw if U > LP

It is clear that the higher the unit weight, U, the higher the intake is. As weights may vary considerably between units, care must be taken when select- ing a value for U .

When data are available on residues in single units and allow for the estimation of the highest residue in a single unit, HRunit, the equations become:

IESTI =      U ×(HRunit_{or HR}unit P )+(LP −U )×(HR or HRP) bw if U ≤ LP U ×(HRunit_{or HR}unit P ) bw if U > LP Case 3

In this case, the number of units is larger than the number of units in a composite sample and the residue level is assumed to be similar to the median of the composite samples from the supervised field trial (e.g. orange juice, tomato soup). When a processed commodity is bulked or blended, the STMRP

value represents the probable highest concentration of residue. IESTI = LP × STMRP

bw

The deterministic IESTI equations are currently used for pesticide registration as illustrated in the red box in Figure 1.3.

1.3.2.3 Decision on pesticide approval and MRL

Data from toxicological tests on the pesticides are used to derive an ‘Acute Reference Dose’ (ARfD). The ARfD is the amount of a chemical that can be consumed at one meal or on one day in the practical certainty, on the basis of all known facts, that no harm will result (JMPR, 2002). It provides a measure of exposure that relates to the hazards occurring during short-term exposure and can be obtained from short- term (repeated daily doses for 14-28 days), sub-chronic and reproductive toxicity tests that provide an estimate of the no-observed-adverse-effect-level (NOAEL), a ‘safe’ dose for a group of experimental animals. The ARfD is obtained by dividing a NOAEL by a safety factor, usually 100, to account for interspecies differences and human variability in sensitivity (Renwick, 2002). This 100-fold safety factor has been attributed to Lehman and Fitzhugh (1954) who stated that ‘the chemical additive should not occur in the total human diet in a quantity greater than 1/100 of the amount that is the maximum safe dosage in long-term animal experiments’ (Ren- wick and Lazarus, 1998; Dorne and Renwick, 2005). Lehman and Fitzhugh (1954) emphasised the arbitrariness of the value by stating that ‘The 100-fold margin of safety is a good target but not an absolute yardstick as a measure of safety. There are no scientic or mathematical means by which we can arrive at an absolute value. However, this factor of 100 appears to be high enough to reduce the hazard of food additives to a minimum and at the same time low enough to allow some use of chemicals which are necessary in food production or processing’. This statement is still valid today despite several attempts to justify the chosen value (Vermeire et al., 1999).

If the consumer intake is below the ARfD, then the proposed MRL and pesticide use is accepted, assuming that the pesticide does not have detrimental effects on non-target organisms. If not (i.e. calculated intake is higher than the ARfD), the use conditions will have to be modified to reduce the residue levels on the commod- ity. Examples of modifications include lowering the dose (providing that it will still be effective), extending the period between treatment and harvest and/or applying the pesticide to a different crop altogether. This process is illustrated in the green

boxes in Figure 1.3.

In this section, we have discussed the deterministic IESTI approach for the pes- ticide registration process, which is currently the most commonly used approach for dietary risk assessment (Paul Hamey, Chemicals Regulation Directorate; per- sonal communication, 21 January 2013). In the next section, we detail alternative probabilistic approaches.