Comparative and Veterinary Pharmacology

Median

Residue 2

first iter

ation

Median

Residue 1

Median

Residuen

MRL 1

MRL 2

MRLn

×

×

×

Metabolism and

pharmacokinetic

studies

Residue

depletion

study using

radiolabelled

drug

Estimation of

the maximum

permissible

residue

Determination

of the maximum

residue limit

(MRL)

Quantify total residue (TR) and

marker residue (MR)

1 st^ iteration

at time t 1

*Dietary Exposure

< Health Standard

Yes No

2 nd^ iteration

at time t 2

Yes No

nth^ iteration

at time tn

Dietary Exposure

< Health Standard

Yes No

Unable to

establish MRL

Establish MRL

t 1 t 2 tn Time after last

treatment

Log marker residue concentration

next iter

ation

next iter

ation

generate more data

revise use pattern

other

* Dietary ExposureEstimate = ResidueMedian × ConsumptionFigure ×Ratio TR/MR

Dietary Exposure

< Health Standard

Identify the maximum permissible residue

Refine the maximum permissible residue

to account for:

good practice in the use of veterinary drugs

availability of analytical method for

residue monitoring

Consider options:

Fig. 1Schematic diagram of the residue evaluation procedure practised by the Joint FAO/WHO
Expert Committee on Food Additives (JECFA). The major elements of the procedure are depicted
aslarge boxes(left) and the desired outcome of each process is identified (large open arrows). The
establishment of maximum residue limits (MRLs) involves determination of the maximum
permissible residue. This involves an iterative approach where residue values at timet 1 are used
to estimate dietary exposure. If the estimated dietary exposure is less than the health standard, then
the maximum permissible residue has been identified. Otherwise the process is repeated with
values from timest 2 totnas required. The maximum permissible residue may be refined
downwards to account for good practice in the use of veterinary drugs and the availability of
suitable residue monitoring methods in establishing the MRL

276 P.T. Reeves