Substance conversion

When concentration data at the level of measured substances have to be converted into concentration data at the level of active substances (or perhaps also inactive substances), then substance conversion rules are specified to provide the rules, the so-called residue definitions. This section describes the basic substance conversion, and then the refinements using available substance authorisations.

For each measured substance in the concentration data, there may be zero or more conversion rules, each one linking to an active or inactive substance. Each rule is represented by a record in the substance conversion data source. Substance conversion rules may specify a link to an exclusive substance or not. For an exclusive conversion it is assumed that only one substance is present in the sample, therefore the measured substance is considered to be just one of the linked substances. Another possibility is that measured substances link to one or more exclusive substances, plus one (non-exclusive) substance that is considered a metabolite of the other exclusive substances. The metabolite can occur together with any of the exclusive substances. It is assumed that either all conversion rules linked to a measured substance are marked as exclusive (case 1), or exactly one rule is marked as exclusive and the others are marked as not exclusive (case 2). If this does not apply for any set of rules linked to a measured substance, data are regarded as erroneous.

Four methods for substance conversion are implemented:

1. Allocate most potent: for each measured substance, the linked substances are restricted to the active substances of interest. The concentration of the measured substance is assigned to the most potent active substance in this set. Potency is specified by the relative potency factors. All other candidate active substances are assigned a zero concentration. I.e., the measured substance concentration is allocated for 100% to the most potent substance specified by the conversion rules and for this allocation, the concentration or LOQ/LOD is multiplied by the molecular weight correction factor.

2. Random allocation: one of the conversion rules is drawn randomly (with equal probability), including the rules of both active and other substances. Then, the rule is used as follows to generate active substance concentrations:

If the conversion rule is marked as exclusive, the concentration or LOQ/LOD is allocated to the linked substance.

If the conversion rule is marked as not exclusive, a proportion p, as specified by the rule, of the concentration or LOQ/LOD is allocated to the linked substance. The remaining proportion (1-p) is allocated to the substance that is linked to the measured substance in a conversion rule marked as exclusive (in this case it is assumed that exactly one record per measured substance is marked as exclusive).

All assigned concentrations are multiplied by the molecular weight correction factor. All unselected candidate substances are assigned a zero concentration.

3. Nominal estimate: the substances specified through the conversion rules are allocated with a nominal value based on all possible conversion rules. This may be regarded as the nominal or average allocation value of the random sampling method.

All conversion rules are marked as exclusive: the measured substance concentration is allocated over all n active substances specified with equal proportions 1/n, accounting for the molecular weight correction factor for all substances.

Precisely one conversion rule is marked exclusive and n conversion rules are marked as not exclusive: the measured substance concentration is allocated over all active substances specified, with a proportion 1/2 + 1/n for the substance belonging to the exclusive conversion rule, and equal proportions 1/n for the other substances, accounting for the molecular weight correction factor for all substances.

4. Allocate all: the concentration of a measured substance is allocated to each active substance associated with the measured substance as if it were the most potent substance. I.e., the same measured substance is allocated to all associated active substances simultaneously. This method is not sensible when using it in a cumulative assessment, but it is of use in substance screening assessments, where in a combined analysis of multiple substances all active substances are considered independently.

Use of substance authorisations in substance conversion

When substance authorisations are available, these can be used to exclude conversions of measured substances to unauthorised substances on a given food. The information is used as follows in the substance conversion procedures:

1. Allocate most potent: the set of candidate active substances from which the most potent active substance is to be drawn is reduced to only the substances with authorised uses. However, if none of the candidate active substances is authorised, then the most potent of the unauthorised substances is selected for active substance allocation.

Table 68 Most toxic allocation of a measured substance to active substances based on RPFs and authorised use
Active substance	RPF	Authorised use	Active substance	RPF	Authorised use	Measured substance allocated to
AS1	1	true	AS2	2	true	AS1
AS1	1	false	AS2	2	true	AS2
AS1	1	true	AS2	2	false	AS1
AS1	1	false	AS2	2	false	AS1

In Table 68, results of most toxic allocation.

2. Random allocation: the set of conversion rules from which to draw is reduced to the rules linking to authorised substances or the non-exclusive substance (thus allowing the selection of a possibly unauthorised metabolite of an authorised substance). If none of the conversion rules links to an authorised substance, then one rule is drawn from the full set of all (unauthorised) conversion rules.

Table 69 Random allocation of a measured substance to active substances based on authorised use
Active substance	RPF	Authorised use	Active substance	RPF	Authorised use	Measured substance allocated to
AS1	1	true	AS2	2	true	AS1 or AS2
AS1	1	false	AS2	2	true	AS2
AS1	1	true	AS2	2	false	AS1
AS1	1	false	AS2	2	false	AS1 or AS2

In Table 69, results of random allocation.

3. Nominal estimate: the set of conversion rules is reduced in the same way as for random active substance allocation. Nominal calculation is performed on the resulting set of conversion rules.

4. Allocate all: For this method, the same rules apply as for allocate most potent. The set of candidate active substances that are to be allocated is reduced to only the substances with authorised uses. Hence, a substance is not allocated when it is not authorised and there is at least one other candidate active substance that is authorised. However, if none of the candidate active substances is authorised, then the most potent of the unauthorised substances is selected for active substance allocation.

Multiple allocations of the same active substance in one sample

In some datasets substance conversion can cause the same active substance to be allocated multiple times in one sample. For example, when an active substance is measured directly, but also a measurement is recorded for a (measured) substance that converts to the active substance. By default, MCRA does not accept such cases, because often it is associated with errors in the data. Therefore, an error will be reported with a message

“Unexpected substance translation in sample xxx: substance X is translated from multiple measured substances.”

However, if such cases are known to exist and accepted in the data, then a method is available to fix duplicate substance allocation inconsistencies. If active substance allocation leads to multiple allocated measurements then the following procedure is implemented for resolving these inconsistencies:

If any measurement is positive or zero then: clone one of these records to create the “aggregate measurement record”; to make this selection deterministic, prefer records that have measured-substance equal to active-substance over other records, and take the record with the highest residue. Update the measured value of the clone with the mean of all positive/zero measurements.
If all allocated active substance measurements are censored, then clone one of the censored values. Here also, records that have measured-substance equal to active-substance are preferred over other records, and then the measurement with the smallest LOQ/LOD is used.

Note that these rules are quite generic. They work quite well even when there are many measurements for the same active substance. In practice, only a few (two) are expected.