Global harmonization of regulatory requirements

Some critical differences in risk assessment procedure lead to confusing situations on a worldwide basis. These differences are due to some very controversial areas of safety issues including the calculation of the acceptable daily intake (ADI), the assignment of the ADI to maximum residue limit (MRL)/tolerance, the validation of the analytical methods needed to regulate drug residues, and the fitness of legislation to toxicology. 

Other particularly controversial issues of hazard and risk assessment that urgently need harmonization refer to the potential impact of residues of antimicrobial drugs on the human gut flora, the impact of bound residues, and the impact of residues at injection site on the calculation of ADIs. 

Emergence of resistance among zoonotic pathogens has become an issue of increasing worldwide concern. While the phenomenon of induction of resistance is well known, there is no evidence for tlie supposed effects in humans in vivo as a result of ingestion of food contaminated with drug residues. At present, no standardized procedure exists to assess such effects, nor, indeed, are the effects themselves described adequately. 

Despite the lack of agreed guidelines for the tests involved, tests do exist and they comprise studies in human volunteers, studies in germ-free rats the intestines of which harbor human gut bacteria, and in vitro studies with bacterial populations. However, the selection of the most appropriate test system remains an open question. All tests investigate minimum inhibitory concentrations (MICs) that can be used in ADI calculations however, such ADI calculations tend to 

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