Harmonization of MRL Setting for Compounds Used Both as Pesticides and as Veterinary Drugs
Maximum Residue Limits
51. The Committee recalled that at the last session it had noted discussions held at the 22nd Session of the Codex Alimentarius Commission, the 29th and 30th Sessions of the Codex Committee on Pesticide Residues (CCPR) and the 1997 JMPR concerning differences in the way the CCRVDF and the CCPR established MRLs. The Committee had generally recognized the need for harmonization of MRL setting for compounds used both as pesticides and veterinary drugs. An informal JECFA/JMPR Harmonization Meeting had been convened in Rome in February 1999 in order to solve differences in residue definitions and related matters and to ensure harmonization and consistency between JECFA and JMPR. The Harmonization Meeting had made a number of recommendations addressed to CCRVDF, CCPR, JECFA and JMPR. The relevant recommendations had been considered by the 1999 JMPR[14] and 54th JECFA[15].
52. The Committee noted the recommendations relevant to the work of this Committee and considered the following specific issues:
Muscle
53. The Committee recognized that the current definition of muscle (“muscle tissues only”) required refinement; the definition of meat differed from country to country and therefore the definition of meat for the purpose of Codex should be broad. The Committee agreed to maintain the current definition of meat. The Committee agreed to amend a proposal of the 54th JECFA for the definition of muscle by replacing the term “meat” with “muscle” and deleting the term “muscular” from the first line.
Fat
54. Noting that there were no definition of fat in the Glossary of Terms and Definitions at present, the Committee agreed to accept a new definition proposed by the 54th JECFA.
Milk
55. The Committee noted that since the 52nd meeting JECFA had proposed MRLs for milk on a weight basis as recommended by the Harmonization Meeting and agreed to this practice.
56. As a consequence to the adoption of the General Standard for the Use of Dairy Terms by the Codex Alimentarius Commission at its 23rd Session, the Committee agreed to accept a new definition of milk as contained in the General Standard and only slightly different from the current definition of milk in the Glossary of Terms and Definitions.
Eggs
57. The Committee agreed to accept a revised definition proposed by JECFA to clarify the current definition of eggs.
Other Issues
58. The agreed texts of the above definitions are contained in Appendix VII of this Report. The Committee noted that as these new or revised definitions would eventually be included in the Glossary of Terms and Definitions in Volume 3 of the Codex Alimentarius, their elaboration should follow the Codex Elaboration Procedure. As there was consensus, the Committee agreed to use the accelerated procedure pending approval of the Executive Committee to initiate new work.
59. The Committee also considered what action should be taken when JECFA and JMPR had recommended MRLs for the same chemical with the same residue/marker definition on the same commodity. Several delegations contended that if an intake estimate(s) did not exceed the ADI the higher MRL should prevail. Some other delegations expressed the view that the MRL that should prevail should be determined case by case. One delegation stated that the higher MRL should be recommended unless other relevant factors were identified. The Committee agreed that where JECFA and JMPR had recommended MRLs for the same chemical with the same residue/marker definition on the same commodity, the higher MRL should be recommended provided that intake of residues did not exceed the ADI.
60. The Committee noted that when MRLs were proposed by both JECFA and JMPR for one compound, dietary exposure assessments were always performed taking into account proposals from both bodies. The Committee recognized the differences between the methods of exposure assessment used by JECFA/CCRVDF and JMPR/CCPR. The Delegation of New Zealand and the Representative of WHO stated that the methodology[16] utilized by JMPR/CCPR was more sophisticated using more refined estimates of food consumption and levels of residues likely to be present in foods if the pesticide had been applied at the maximum of good agricultural practice. They suggested that the same methodology should also be used by JECFA/CCRVDF.
Abamectin
Carazolol
Chlortetracycline/Oxytetracycline/Tetracycline
Clenbuterol
Cyfluthrin
a-Cypermethrin and Cypermethrin
Danofloxacin
Deltamethrin
Dexamethasone
Dihydrostreptomycin/Streptomycin
Doramectin
Eprinomectin
Estradiol-17b, Progesterone and Testosterone
Flumequine
Gentamicin
Imodocarb
Neomycin
Phoxim
Porcine Somatotropin
Sarafloxacin
Thiamphenicol
61. The Committee agreed not to consider new recommendations of the 54th JECFA as the Summary and Conclusions of that meeting became available only at the present session.
62. The Committee noted that at present there was one ADI for abamectin recommended by the 1997 JMPR. The Delegation of Portugal, speaking on behalf of the member states of the European Union, reiterated their opposition to the basis of the setting of the ADI by the 1997 JMPR[18].
63. The Committee noted that the 54th JECFA had not harmonized the residue definition with the one recommended by JMPR. The Delegation of Canada proposed that the Committee should use the broader residue definition recommended by JMPR, which includes photodegradation isomers, and advance the draft MRLs to Step 8. However, the Committee decided to retain the current definition and to retain the draft MRLs at Step 7.
64. The Committee decided to retain the draft MRLs at Step 7 as JECFA pointed out and some delegations considered that the use of this non-selective potent b-adrenoreceptor blocker in food animals immediately prior to slaughter was inconsistent with the safe use of veterinary drugs and resulted in residues at injection site with the potential to cause acute reactions if consumed.
65. The Delegation of Portugal, speaking on behalf of the member states of the European Union, expressed the opinion that setting the ADI based on microbiological in vivo studies without applying safety factor was unacceptable. Some other delegations stated that the use of safety factor was not relevant to the ADI setting because the endpoint was based on studies in target bacterial species, not in mammalian species, which were extremely sensitive and conservative. It was generally recognized that ADI setting based on microbiological studies was still under development and not yet validated. Since it was considered that there was insufficient expertise in this Committee to fully consider this issue, the Committee requested the drafting group that was entrusted to prepare a paper on risk analysis principles and methodologies (see para. 19) to review the use of microbiological endpoints for the ADI setting from the point of view of risk assessment policy.
66. Some delegations mentioned that MRLs for these substances were necessary for developing countries and the holding of these MRLs at Step 7 would have adverse implications for these countries.
67. The Committee noted that the TMDI was about 10% of the ADI.
68. The Committee decided to retain the draft MRLs at Step 7. In making this decision, the Committee requested the European Community to send information on the setting of an ADI based on microbiological endpoint to JECFA with the understanding that if no information was received by JECFA by the next session, the Committee would consider advancement of the MRLs to Step 8.
69. Several delegations expressed their concerns about the use of clenbuterol in food animals especially in relation to potential/current abuse of this substance, difficulties in controlling the abuse and substantial effects on meat quality by abuse. These delegations proposed withdrawal of the proposed draft MRLs except that for milk.
70. Several other delegations expressed the view that the control of use was achievable and the above was not a relevant reason for withdrawal, and opposed the withdrawal. As a compromise, the Committee agreed to retain the proposed draft MRLs except that for milk at Step 4.
71. Since it was considered that there was less likelihood of abusing clenbuterol on milking cattle, and a method of analysis existed that was capable of quantifying clenbuterol in milk at the level of 0.05 µg/kg, the Committee agreed to advance the proposed draft MRL in milk to Step 5.
72. The Committee noted that there was now harmonization between the MRLs being considered for veterinary uses and those for pesticide uses. However, the European Community mentioned that their provisional ADI was established at 1 µg/kg-bw based on the NOEL of inclined plane test in rats using a safety factor of 10. This was significantly lower than the ADI recommended by JECFA based on the NOEL of 2-year toxicity study in rats using a safety factor of 100. The WHO Joint Secretary of JECFA explained that JECFA often had difficulty interpreting the results of inclined plane test and this text had not been validated. The European Community was requested to send its scientific data to JECFA.
73. The Committee decided to retain the draft MRLs at Step 7 with the understanding that if no new information was received by JECFA by the next session, the Committee would consider advancing the MRLs to Step 8.
74. The Committee noted that the 54th JECFA had not extended the draft temporary MRLs for these substances at Step 8 as information required by the 47th JECFA had not been provided and there had been no indication of its future submission.
75. The Committee decided to withdraw these temporary MRLs.
76. The Committee agreed to advance the draft MRLs to Step 8.
77. The acting FAO Joint Secretary to JECFA explained that no residues had been detected in muscle of cattle, sheep, chicken and salmon and cattle milk and chicken eggs; MRLs for these species/tissue combinations were based on two times the limit of quantification of the analytical method; and they were recommended for guidance only and not included in the TMDI calculation. The Delegation of Portugal, speaking on behalf of the member states of the European Union, mentioned the differences in the approach to MRL setting between JECFA and the European Community including differences in the evaluation of analytical methods and in the residue definitions.
78. The Committee decided to retain the proposed draft MRLs at Step 4. The Committee requested the European Community to forward scientific information in support of their concerns to JECFA with the understanding that if no information was submitted to JECFA by the next session, the Committee would consider advancement of the MRLs.
79. Noting the recommendations of the 48th and 50th JECFA, the Committee decided to withdraw the draft temporary MRLs. This decision was based on the lack of a suitable analytical method for regulatory monitoring.
80. The Committee agreed to advance the proposed draft revised and amended MRLs to Step 5 with a recommendation to omit Steps 6 and 7 for adoption at Step 8.
81. The Committee agreed to advance the proposed draft MRLs to Step 5 with a recommendation to omit Steps 6 and 7 for adoption at Step 8. The Committee noted that the statement “high concentration of residues at the injection sites” was an advisory note for governments and was not based on quantitative aspects.
82. The Delegation of Portugal, speaking on behalf of the member states of the European Union, contended that their ADI was established using a safety factor of 200 in the absence of toxicological data on CF-1 mice. The WHO Joint Secretary to JECFA stated that although JECFA previously had used the same approach as that of the Committee for Veterinary Medicinal Products of the EU, it had come to the conclusion that CF-1 mice were not an appropriate species for assessing toxicology for humans and should not be used for setting the ADI. It was noted that the TMDI was slightly higher than the ADI of the European Community.
83. The Committee decided to retain the draft MRLs at Step 7. The Committee requested the European Community to send the information regarding the above to JECFA with the understanding that if no new information was received by JECFA by the next session the Committee would consider advancement of the MRLs.
84. Recognizing that this Committee had not requested the re-evaluation of these substances and that the new MRLs recommended by the 52nd JECFA did not differ significantly from the current MRLs, the Committee decided not to consider these new recommendations.
85. The Committee noted that the 54th JECFA had converted temporary MRLs to full MRLs and had modified MRLs for liver from 1000 µg/kg (T) to 500 µg/kg.
86. The Delegation of Portugal, speaking on behalf of the member states of the European Union, expressed objection to the approach taken by JECFA in deriving the ADI. While their ADI was based on the MIC50 of the most sensitive microorganism, E. coli, the ADI recommended by JECFA was based on the MIC50 of the most predominant human gut flora, Fusobacterium and Clostridium. The WHO Joint Secretary to JECFA stated that at a recent meeting of JECFA it was concluded that it was inappropriate to base an ADI on studies using E. coli, the most sensitive species but not regarded as one of dominant species in human gut flora. It further concluded to use the most dominant microorganisms for the ADI setting.
87. The Committee decided to retain the draft MRLs at Step 7. The Committee requested the European Community to forward their data and comments regarding the setting of the ADI with the understanding that if no information was received by JECFA by the next session, the Committee would consider advancement of the MRLs to Step 8.
88. The Committee agreed to advance the draft MRLs to Step 8.
89. The Committee agreed to advance the draft temporary MRLs to Step 8.
90. The Committee noted that the re-evaluation of neomycin by JECFA was not initiated by the Committee by including it in the Priority List and that the data provided was for an injectable formulation of neomycin. The Committee agreed to advance the proposed draft revised and amended MRL to Step 5. Recognizing that the proposed revised MRLs were based on an injectable formulation, the Committee agreed to seek information on the registration of injectable neomycin products as well as how they were used with respect to Good Practices in the Use of Veterinary Drugs. This information would be sought from governments by way of a Codex circular letter.
91. The Committee decided to advance the proposed draft MRLs to Step 5 noting that phoxim was being reviewed by the European Community.
92. The Delegation of Portugal, speaking on behalf of the member states of the European Union, making reference to “Good Veterinary Practice”, stated that since the substance was not used to treat or prevent disease, its use was outside of good practices and discussions on the MRLs should await the consideration on “other legitimate factors” by the Codex Committee on General Principles. The Committee noted that the definitions of “Veterinary Drug” and “Good Practice in the Use of Veterinary Drugs” included uses other than therapeutic, such as prophylactic and for modification of physiological functions.
93. Several delegations requested advancing the MRLs to Step 5 as they felt that the JECFA evaluation was of good quality and the result of risk assessment indicated that there was no risk to the health of consumers.
94. The Committee agreed to advance the proposed draft MRLs to Step 5 with the understanding that their further advancement was subject to the outcome of discussion on “other legitimate factors” by the Codex Committee on General Principles.
95. The Committee agreed to advance the draft MRLs to Step 8.
96. The Committee advanced the proposed draft temporary MRLs to Step 5. As the 52nd JECFA had not received required data and had proposed withdrawal of the draft MRLs at Step 7, the Committee agreed to withdraw these draft MRLs.
Other matters
97. The Observer from COMISA expressed disappointment at the retention of so many MRLs and urged the Committee to proceed more expeditiously. He suggested that the Committee should carry out a performance review of its standard setting work. He added that the too slow progress was one of the reasons why some companies had become reluctant to be a sponsor of data; and there should be a better balance between caution and progress while meeting the requirement of protecting the health of consumers.
