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3.3 Assessment of chronic dietary risk of dithiocarbamate pesticides

In response to a question raised at the 29th Session of the CCPR, the present Meeting discussed the principles used in assessing the chronic dietary risk of dithiocarbamate pesticides. The dithiocarbamates considered by the JMPR and Codex consist of eight agricultural pesticides which are listed as a group on the basis of a common analytical method for their determination. Residues of ferbam, mancozeb, maneb, metiram, propineb, thiram, ziram, and zineb are all determined by a method that depends upon the generation of carbon disulfide. The Codex MRLs for these pesticides are grouped under the heading Dithiocarbamates (105),.

After reviewing previous JMPR reports the Meeting concluded that the dithiocarbamate pesticides should be divided into two groups on the basis of toxicity. The ADIs for mancozeb, maneb, metiram, propineb, and zineb are based on thyroid toxicity; the 1993 JMPR allocated a group ADI of 0 - 0.03 mg/kg bw for mancozeb, maneb, metiram, and zineb. The thyroid toxicity of these compounds is mediated by their common metabolite, ethylenethiourea (ETU), and an ADI of 0 - 0.004 mg/kg bw has been allocated to this compound. The 1993 JMPR also allocated ADIs of 0 - 0.007 mg/kg bw to propineb and 0 - 0.0002 mg/kg bw to its metabolite propylenethiourea (PTU).

After reviewing previous JMPR reports on thiram, ferbam, and ziram, the Meeting concluded that their toxicity was similar enough for them to be considered together, but that this group was distinct from the other group of dithiocarbamates since the toxic end-point upon which their ADIs are based is not associated with thyroid toxicity. Ferbam and ziram were evaluated by the 1996 JMPR, when a group ADI of 0 - 0.003 mg/kg bw was allocated. The current ADI of 0-0.01 mg/kg bw for thiram was allocated by the 1992 JMPR.

On the basis of these considerations the Meeting recommended that the chronic dietary risk for the two groups of dithiocarbamate pesticides be assessed using STMR levels and other factors, as described in Guidelines for predicting dietary intake of pesticide residues (WHO, 1997. For those commodities potentially containing more than one pesticide for which residue data have been accepted by the JMPR, the risk assessment should be based on the pesticide that contributes most to the estimated intake in relation to its ADI.

The Meeting drew attention to the use of data on processing in assessing the 'thyroid-active' dithiocarbamates. Processing food commodities containing residues of these pesticides generally decreases the amount of the parent pesticide and increases that of ETU or PTU. This has clear implications for risk assessment, in view of the greater toxicity of ETU and particularly PTU. ETU is generally short-lived when applied to plant leaves in plant metabolism studies and it is rapidly degraded by UV radiation1. In supervised trials with ethylenebisdithiocarbamates (EBDCs), the ETU residues in raw agricultural commodities were generally £ 0.1 mg/kg or £ the LOD of 0.01-0.02 mg/kg. In some cases ETU residues were reported to be an artifact of the analysis, because a small percentage of EBDC residues can be converted to ETU during their determination, especially if the method includes a heating step. The ETU levels in processed commodities depend on the levels of the parent EBDC present at crucial stages during heating. For an overall risk assessment of 'thyroid-active' dithiocarbamates, the Meeting agreed that it is necessary to combine not only the intake of different parent pesticides but also the intake of ETU or PTU. It recommended that an ADI adjustment approach be used, and that an example of this approach should be developed in 1998.

1 JMPR Residue Evaluations, 1993, pages 354-5.

The Meeting recognized that it is difficult to incorporate data on processing into risk assessments carried out at the international level, because data on food consumption are not always available. Processing factors for commodities for which consumption data are not provided by GEMS/Food may be incorporated into risk assessments at the national level as appropriate.

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