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Regulatory Aspects for the Drugs and Chemicals Used in Food-Producing Animals Chapter | 7 123

VetBooks.ir or mADI) exposure scenario that on given day, the is established for a defined period and only in those cases
where there are no grounds for supposing that residues of
ingested ADI is loaded into an intestinal tract that already
has comparable concentrations of drug spanning the intes-
the substance at the level proposed will present a hazard
tine due to ingestion from daily consumption of the drug to the health of the consumer but where further informa-
at the ADI level of ingestion. What is critical in delineat- tion is still required in order to finalize the evaluation of
ing this comparison of residue “loading,” is the observa- the substance; (3) the absence of the need to establish an
tion that the components contained within a single meal MRL (i.e., no MRL is required for substances where resi-
do not enter the colon as a bolus (Cerniglia et al., 2016). dues at the predicted levels do not pose a hazard to the
While this bolus approach (220 g) may be appropriate as health of the consumer); and (4) a prohibition on the
a conservative means to derive a safe daily ingestion rate administration of a substance. Those substances included
for a lifetime mADI, the 220 g bolus assumption underes- in Annex I, II, or III and the amount of residue are not
timates the temporary dilution concept (i.e., ingestion of a considered to present a safety concern for human health.
residue in a single acute dose meal’s entry into the intesti- Those substances included in Annex I, II, or III of the
nal tract). Currently, this is elaborating guidance on Council Regulation (EEC) No 90/2377 (EEC, 1990) are
approaches to determine the ARD of veterinary drug from listed in the Annex of Commission Regulation (EC) No.
a toxicological and microbiological perspective (FDA, 37/2010 (EC, 2010) (Table 7.1), allowed substances,
2013). where there are listed the pharmacologically active sub-
To establish MRLs for a given drug requires provision stance, marker residue, animal species, MRL value, target
of the following data: knowledge of dosage schedule tissues, other provisions (according to Article 14(7) of
(amount, dose interval, and duration) and administration Regulation (EC) No. 470/2009, EC, 2009a) and therapeu-
route; metabolic and pharmacokinetic data in laboratory tic classification, and Table 7.2 (prohibited substances)
animals and each of the target food producing species; (where an MRL cannot be established). These substances
distribution and residue depletion data for the major edi- must not be used in veterinary medicines for food-
ble tissue (i.e., muscle, fat, liver, and kidney) in each tar- producing animals or in biocidal products for use in ani-
get species using a radiolabeled drug; validated analytical mal husbandry (Table 7.9). This classification substitutes
methods for detection and quantitation of residues, includ- the four annexes of the Council Regulation (EEC) No.
ing marker residue; and data defining the effect of resi- 2377/90.
dues on food processing. Under EU legislation (article 14
(2) of Regulation (EC) No. 470/2009 (EC, 2009a)) the Establishment of Codex Maximum Residue
classification of pharmacologically active substances shall Limits for Drugs and Feed Additives
also establish, in relation to each such substance, and,
where appropriate, specific food stuffs or species. The JECFA is an international expert scientific committee
Substances that may be used in veterinary medicines for that is administered jointly by the Food and Agricultural
food-producing species or biocidal products for use in Organization of the United Nations (FAO) and the World
animal husbandry are listed in food stuffs Table 7.1 Health Organization (WHO). JECFA serves as an inde-
(allowed substances) with the following information: (1) pendent scientific committee that performs RAs and pro-
the definitive MRL to be applied to each food commod- vides advice to FAO, WHO, and the member countries of
ity; (2) a provisional MRL to be applied to each food both organizations. Requests for scientific advice are for
commodity (pending further data). The provisional MRL the main part directed through the CAC in their work to

TABLE 7.9 Active Substances Are Classified Under Four Categories
Regulation (EC) No. 470/2009 Regulation (EEC) No. 2377/90
(a) A maximum residue limit Annex I. List of pharmacologically active substances for which maximum residue limits
have been fixed
(b) A provisional maximum residue limit Annex III. List of pharmacologically active substances used in veterinary medicinal
products for which provisional maximum residue limits have been fixed
(c) The absence of the need to establish a Annex II. List of substances not subject to maximum residue limits
maximum residue limit
(d) A prohibition on the administration of Annex IV. List of pharmacologically active substances for which no maximum levels
a substance can be fixed