Residue analysis of dithiocarbamates in food
Planned changes to maximum residue levels and residue definition
April 2025. In April 2024, the European Commission published a draft amending regulation Plan/2023/2019[1], which aims to adapt the maximum residue levels and residue definition for the dithiocarbamate pesticide group in the existing regulation Regulation (EC) No 396/2005. The amendments are intended to take into account future confounding factors in the analysis of dithiocarbamates, such as natural sources of carbon disulphide (CS2).
We give you a compact overview:
- Maximum residue levels of dithiocarbamates in food
- Area of application, mechanism of action and toxicological significance
- Peculiaritiesof the analytical determination of dithiocarbamates
- Legal classification
- Contact our experts
Maximum residue levels of dithiocarbamates in food
The use of pesticides is an integral part of conventional agriculture. In order to harmonise maximum residue levels (MRLs), the European Food Safety Authority (EFSA) has established MRLs at European level under Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin. In accordance with Article 3(d), these MRLs represent the maximum level of a pesticide residue on food and feed that is necessary to protect vulnerable consumers. However, MRLs are not fixed and can be adapted to the data situation through amending regulations, depending on the approval of the pesticides concerned in the EU and the re-evaluation and risk assessment of each substance. Such an amending regulation is currently in place for dithiocarbamates, among others.
Area of application, mechanism of action and toxicological significance
The dithiocarbamates are a class of fungicides that have been widely used since the beginning of the 20th century and are commonly used in orchards, as well as on tea and tobacco[2]. The class of compounds describes derivatives of dimethyldithiocarbamic acid and alkylene-bis-dithiocarbamic acids. The chemical structure of these pesticide compounds includes a metal ion, nitrogen, carbon and sulphur. The mechanism of action is based on the dithiocarbamate anions formed during the metabolism of the dithiocarbamates. These are highly reactive and form chelates which inhibit catalytic and regulatory groups of enzymes[3,4,5].
Toxic effects can occur after dermal, inhalative or oral uptake of dithiocarbamates. The main exposure has been described by oral uptake of the fungicides, but occupational exposure may also be an important source of exposure. In addition to their use as fungicides, some dithiocarbamates are used in industrial manufacturing processes such as the vulcanisation of latex gloves. Due to their lipophilic properties, dithiocarbamates are easily absorbed into cells[6,7,8]. Of toxicological concern, however, are the degradation products of dithiocarbamates, such as ethylene thiourea (ETU), for which thyroid or endocrine disrupting, teratogenic and carcinogenic effects have been described[8,9,10,11].
Peculiarities of the analytical determination of dithiocarbamates
Due to the complexity of the class and the physico-chemical properties, dithiocarbamates are usually quantified indirectly via carbon disulphide (CS2), which is present in all dithiocarbamates. This is determined analytically, e.g. by the DFG S15 method. For analysis, samples are heated in an acidic salt solution, which releases the volatile CS2 and allows it to be distilled off. The CS2 concentration is then determined by UV spectroscopy.
However, natural sources of CS2 such as brassicaceae and allium plants as well as the avoidance of vulcanised latex gloves should also be considered in the analysis and evaluation process. In addition, both during sample preparation and in the laboratory, it must be kept in mind that dithiocarbamates can degrade rapidly in some cases. Depending on the type and length of storage of the samples, CS2 precursors can be formed, which can lead to a loss of CS2, which influences the result of the analysis[12].
Legal classification
For the currently valid residue definition "dithiocarbamates (dithiocarbamates expressed as CS2, including maneb, mancozeb, metiram, propineb, thiram and ziram)" the MRLs are regulated in Regulation (EC) No 2017/171. As part of the planned amending Regulation, in addition to the adaptation of the MRLs, the residue definition will be changed to "dithiocarbamates (dithiocarbamates, determined and expressed as CS2)". Since it is not possible to draw direct analytical conclusions on the individual substances used and only CS2 is determined.
Since natural occuring CS2 in some plants could give the impression that dithiocarbamates were being used, the proposed amending regulation will also take into account natural CS2 concentrations when setting MRLs. It is planned to increase the relevant MRLs to naturally occurring levels identified in an evaluation of CS2 levels in organic food. For crop-MRL combinations where a risk to consumers cannot be excluded compared to the previous MRLs, appropriate MRL reductions will be enforced.
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Sources
[1] Commission Regulation draft intended to amend Annexes II and III to Regulation (EC) No 396/2005 of the European Parliament and of the Council as regards maximum residue levels for dithiocarbamates in or on certain products
[2] Federal Office of Consumer Protection and Food Safety (2022). “Pesticide residues in food”. National reporting 2020 Federal Republic of Germany – condensed version
[3] Rubino, F., E. Mrema, and C. Colosio (2014). "Pesticide residues: dithiocarbamates." Encyclopedia of food safety. Elsevier. pp. 5-10.
[4] Morrison, B. W., Doudican, N. A., Patel, K. R., & Orlow, S. J. (2010). Disulfiram induces copper-dependent stimulation of reactive oxygen species and activation of the extrinsic apoptotic pathway in melanoma. Melanoma Research. Vol. 20, pp. 11-20
[5] Campanale C, Triozzi M, Ragonese A, Losacco D, Massarelli C. (2023). Dithiocarbamates: Properties, Methodological Approaches and Challenges to Their Control. Toxics. doi: 10.3390/toxics11100851. PMID: 37888701; PMCID: PMC10610574.
[6] Rath, Narayan & Rasaputra, Komal & Liyanage, Rohana & Huff, Gerry & Huff, William. (2011). Dithiocarbamate Toxicity - An Appraisal. 10.5772/18307
[7] National Institute for Occupational Safety and Health. (1990). National Occupational Exposure Survey (1981-83). Retrieved from https://www.cdc.gov/niosh/docs/89-102/89-102.pdf
[8] Mutic AD, Baker BJ, McCauley LA. (2017). Deleterious Effects From Occupational Exposure to Ethylene Thiourea in Pregnant Women. Workplace Health & Safety. doi:10.1177/2165079916687312
[9] Edwards, I.R., D.H. Ferry, and Temple W.A. (1991). Fungicides and related compounds. In:Handbook of Pesticide Toxicology, v3, W.J. Hayes, Jr. and E. R. Laws, Jr. editors AcademicPress, San Diego, CA. Pp 1409-1470
[10] DeCaprio, A. P., Spink, D. C., Chen, X., Fowke, J. H., Zhu, M., & Bank, S. (1992).Characterization of isothiocyanates, thioureas, and other lysine adduction products in carbon disulfide-treated peptides and protein. Chemical Research in Toxicology. Vol. 5, pp. 496-504
[11] Houeto, P., Bindoula, G., & Hoffman, J. R. (1995). Ethylenebisdithiocarbamates and ethylenethiourea: possible human health hazards. Environmental Health Perspectives. Vol. 103, pp. 568-573
[12] WHO (1988). Environmental Health Criteria 78 Dithiocarbamate Pesticides, Ethylenethiourea and Propylenethiourea: A General Introduction. International Programme On Chemical Safety; Geneva, Switzerland
