non-genotoxic carcinogens may be regulated using a threshold approach such as
the NOEL-safety factor approach described above.
A critical consideration in the hazard characterisation step is that animal toxico-
logical studies are conducted at concentrations several orders of magnitude higher
than the concentration of chemical residues likely to be present in food. Before
establishing the upper limit of the range of ADI of the residue, it is therefore
necessary to determine the significance of responses detected in high-dose animal
toxicological studies for low-dose human exposures. At the conclusion of this step,
the upper limit of the range of ADI of the hazardous agent is known. It is then
assumed that dietary intakes over a lifetime at or below this limit would not pose an
appreciable risk to the health of consumers.
2.1.3 Exposure Assessment
The dietary intake of drug residues in food is estimated from the amount of the food
commodity consumed, the concentration of residues present in the food consumed,
and the ratio of marker residue to total residues. Only the first of these factors will
be discussed here; the other two factors are discussed under risk characterisation
later in this chapter.
Food consumption factors for the exposure assessment of veterinary drug resi-
dues are sourced from a widely used model. The model comprises 300 g of muscle
(or muscle and skin in natural proportions in the case of fish), 100 g of liver, 50 g of
kidney, 50 g of fat, 1.5 l of milk, 100 g of eggs and 20 g of honey. Fat in the model is
replaced by the same amount of fat and skin in natural proportions in the case of
pigs and poultry.
While all jurisdictions source food consumption factors from the model
described above, the factors are used differently. Regulatory agencies in the
European Union (EU) estimate the theoretical maximum daily intake (TMDI) for
a 60-kg person according to (1):
TMDI¼SðÞDaily IntakeiMRLiTRi=MRi (1)where Daily Intakei(kg) is the daily consumption as defined in the model food
basket; MRLiis the MRL (mg/kg) for muscle, fat, liver, kidney, eggs and honey;
TRiis the total residue concentration (or pharmacological or microbiological
activity where relevant) and MRiis the marker residue concentration (or phar-
macological or microbiological activity where relevant) in the same tissues and
commodities.
The JECFA adopted a new approach for estimating chronic dietary intake at
its 66th meeting (WHO 2006 ). The estimated dietary intake (EDI) differs from the
TMDI inasmuch as MRL used in the TMDI calculation is replaced with the median
concentration of residue in the EDI calculation. In justifying the new approach, the
JECFA contended that the MRL is not a realistic estimate of the residue concentra-
tion in a chronic intake scenario because it represents the estimated upper limit of a
Drug Residues 271