MRLs - Other Considerations

In many cases, maximrun residue limits (MRLs) exist for veterinary drugs and the analytical methods must be capable of measming below such MRLs. Since MRLs vary considerably, the sensitivity requirements of the various methods also vary widely. Typically, MRLs for veterinary drug residues vary from Imgkg (ppm) to Ipgkg (ppb) (Table 1) or, in the case of banned substances, to no detectable residue . Where no detectable residue is specified, it is common to declare an action limit or a limit of decision for use by regulatory agencies this is not strictly scientifically based and takes into account other aspects such as the sensitivity of a suitable confirmatory technique and policy requirements. 

The extent of validation of confirmatory techniques is currently under consideration. Qne approach is that the extent of validation may be smaller than for the enforcement method. In principle, validation in triplicate at the relevant concentration level (LOQ or MRL) is sufficient. In the case where an MRL is set for multiple crops, a single validation in all representative crop groups is sufficient. A confirmatory method for residues in air is not required if a corresponding method was submitted for the other sample matrices. This approach is realized in Germany. ... 

An example of the application of this procedure for testing the equivalence of the albendazole or ivermectin MRLs for which differences exist between the United States and JECFA is presented in Table 12.5. Differences between US and JECFA MRLs for albendazole are due to use of different safety factors and to the JECFA consideration of good veterinary practice. That is, JECFA considered practical conditions of use of the drug and set MRLs consistent with that use accordingly, the entire ADI is likely not to be consumed. On the other hand, the United States always uses the entire ADI in setting MRLs for edible tissues. 

No oral MRL has been derived for chromium(VI) or chromium(III) because a NOAEL for reproductive effects has not been adequately characterized. Additional studies are needed to identify a threshold for toxicity and establish dose-response relationships. However, any MRL derived for the oral route would have to take into consideration the essentiality of chromium. No dermal studies of intermediate duration in animals were located. The toxicity of intermediate-duration exposure to chromium compounds is relatively well characterized for the oral and inhalation routes. Dermal studies would be useful to determine possible target organs other than the skin. There are populations surrounding hazardous waste sites that might be exposed to the substance for similar durations. 

Public Comment on an MRL Based on Other Endpoints. One public comment suggested that ATSDR consider basing its chronic oral MRL on the reproductive and developmental effects observed in an animal study by Arnold (Arnold et al. 1995). The Submitter argued that the results of this study suggest an MRL of 0.5 pg/kg/day. None of the panelists advocated the use of this MRL, presumably because the MRLs based on the studies discussed in Sections 3.7.1 and 3.7.2 are both considerably lower than the MRL derived using the Arnold study. 

Precision, which quantifies the variation between replicated measurements on test portions from the same sample material, is also an important consideration in determining when a residue in a sample should be considered to exceed a MRL or other regulatory action limit. Precision of a method is usually expressed in terms of the within-laboratory variation (repeatability) and the between-laboratory variability (reproducibility) when the method has been subjected to a multi-laboratory trial. For a single-laboratory method validation, precision should be determined from experiments conducted on different days, using a minimum of six different tissue pools, different reagent batches, preferably different equipment, and so on, and preferably by different analysts Repeatability of results when determined within a single laboratory but based on results from multiple analysts is termed intermediate precision Precision of a method is usually expressed as the standard deviation. Another useful term is relative standard deviation, or coefficient of variation (the standard deviation divided by the absolute value of the arithmetic mean result, multiplied by 100 and expressed as a percentage). 

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