high percentile (commonly the 95%) of the distribution of marker residue present in
tissues of treated animals. By comparison, the median residue concentration repre-
sents the best point estimate of a central tendency over a prolonged period.
The EDI (mg) for a 60-kg person is determined as follows:
EDI¼SðÞDaily IntakeiMedian residue concentrationiTRi=MRi (2)where Daily Intakei(kg) is the daily consumption as defined in the model food
basket; median residue concentrationiis the median residue concentration (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 pharmacological or microbiological activity where
relevant) in the same tissues and commodities.
The actual difference in value of the TMDI and the EDI varies on a case-by-case
basis. For example, the FAO report of the 66th meeting of the JECFA cites TMDI
and EDI values of 229mg and 56.9mg, respectively, for colistin and 55mg and
29.1mg, respectively, for erythromycin.
A recent paper published by the EMEA/CVMP noted that the EDI calculation
was developed for the purpose of estimating the chronic daily intake and recom-
mended the development of a complementary procedure for estimating acute daily
intake (EMEA-CVMP2008a). This recognises that many veterinary drugs elicit
acute pharmacological effects. In Australia, the EDI calculation developed by the
JECFA for estimating chronic daily intakes has been adopted and is used in
conjunction with a procedure for estimating acute dietary intake. The latter has
been described elsewhere (Reeves 2007 ). Briefly, the national estimated short-term
intake (NESTI) of residues is calculated and reconciled with the ARfD of the
veterinary drug. Separate NESTI calculations are performed for each of the edible
tissues, and milk and/or eggs where applicable. This procedure is therefore dissimi-
lar to an EDI calculation in which all edible tissues, and milk and/or eggs where
applicable, are incorporated in a single calculation. Values of NESTI are estimated
as the product of the 97.5% consumption value for Australian consumers for each
edible tissue, and milk and/or eggs where applicable, and the highest residue
concentrations reported in residue depletion trials. MRLs are not advanced if the
point estimate of short-term dietary consumption exceeds the ARfD at the with-
drawal period.
The procedure practised by the United States Food and Drug Administration (US
FDA) for calculating dietary exposure is fundamentally different to those used to
calculate the TMDI and the EDI. As residues are partitioned at an early step in the
procedure for calculating a safe concentration of total residues, it is unnecessary to
reconcile dietary intake and the ADI at a later stage. The US FDA approach uses the
same food consumption factors as JECFA; however, it applies them differently. The
US FDA assumes that if a person consumes 300 g of muscle tissue, then the person
will not consume an allocation of liver or kidney but may consume a full allocation
of milk and eggs. A safe concentration of total residues for edible tissues, and for
milk and eggs where applicable, is initially calculated on the basis of the ADI and
272 P.T. Reeves