DITHIOCARBAMATES JMPR 1974
The dimethyl and the ethylene-bis-dithiocarbamates were evaluated
by the Joint Meeting in 1965, 1967 and 1970 (FAO/WHO 1965, 1968,
1971). These meetings listed requirements for information on methods
of analysis, pathways of breakdown or metabolism in plants and in
animals, studies on possible carcinogenic effects, effects on thyroid
function, effects on reticuloendothelial and haematopoietic systems
and effects on reproductive physiology. Much of the latter information
had not become available for consideration at the Meeting.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
For the dimethyldithiocarbamates (ferbam, thiram, and ziram), new
data showing a teratogenic effect with ziram and thiram and
chromosomal aberrations with ziram (Antonovic et al., 1971) have
become available. Ziram, thiram and ferbam have also been shown to be
nitrosated in vitro and in vivo and may therefore be capable of
forming nitrosamines (IARC Monograph, 1974).
In the case of the ethylenebisdithiocarbamates (mancozeb, maneb,
nabam, and zineb), reports have been received that these fungicides
may be teratogenic (Petrova-Vergieva and Ivanova-Chemishanska, 1973).
Furthermore, ethylenethiourea, a major breakdown and metabolic product
of these pesticides (FAO/WHO, 1971; Truhaut et al., 1973), is
teratogenic, mutagenic, and produces thyroid carcinomas and liver
tumours in mice and rats (Graham et al., 1973; Sram and Benes, 1974;
IARC Monograph, 1974). There has been a suggestion that with prolonged
oral administration zineb, maneb, and ziram induce pathological
alterations resembling precancerous changes in the lung of rats
(Antonovic et al., 1971).
The Meeting recognized that current needs for these pesticides in
food production entail their extensive use. Until methods of residue
analysis that distinguish between the two groups of dithiocarbamates
come into general use, the Meeting decided to allocate a new temporary
ADI to all dithiocarbamate fungicides.
On the basis of the above findings it was decided to lower the
value of the temporary ADI. The new lower temporary ADI of 0.005 mg/kg
is based on a larger safety margin from the no-effect levels specified
by the 1970 Meeting, (FAO/WHO, 1971). In extending the temporary ADI
for the dithiocarbamates until 1977, the Meeting recommended that the
temporary ADIs should be withdrawn if required data are not
RESIDUES IN FOOD AND THEIR EVALUATION
The Meeting examined available information on various
ethylenebisdithiocarbamate fungicides but data on compounds other than
mancozeb were lacking. Results of numerous studies on mancozeb were
evaluated and a separate monograph was prepared.
Methods of analysis are available which determine total
ethylenebisdithiocarbamates (EBDTCs) but do not distinguish between
them. Methods which determine the ethylenediamine moiety are preferred
since these distinguish EBDTC residues from dimethyldithiocarbamate
(DMDTC) residues. A separate determination of the metabolite
ethylenethiourea (ETU) is necessary. The suitability of available
methods is discussed in detail in the monograph on mancozeb.
Residue limits were recommended for mancozeb on a number of raw
agricultural commodities. In the absence of the necessary information
on the level and nature of residues resulting from approved uses of
maneb, zineb, metiram etc. however, the Meeting was unable to
recommend residue limits for these pesticides. Further information on
these compounds is required.
FURTHER WORK OR INFORMATION
REQUIRED (by 1977)
1. Residue studies in which both the ethylenediamine moiety and
ethylenethiourea (ETU) are separately determined.
2. Further studies on the fate of residues during the preparation
and processing of foods with particular reference to their
conversion to ETU.
Antonovic, E.A. et al. (1971) [Toxicity of dithiocarbamates and their
fate in warm-blooded animals.] In: Proceedings on Toxicology and
Analytical Chemistry of Dithiocarbamates, Dubrovnik, p. 1-143.
FAO/WHO. (1965) Evaluation of the toxicity of pesticide residues in
food. FAO Meeting Report No. PL/1965/10/1; WHO/Food Add./27.65.
FAO/WHO. (1968) 1967 Evaluations of some pesticide residues in food.
FAO/PL/1967/M/11/1; WHO/Food Add./68.30.
FAO/WHO. (1971) 1970 Evaluations of some pesticide residues in food.
AGP/1970/M/12/1; WHO/Food Add./71.42.
IARC. (1974) IARC monographs on the evaluation of carcinogenic risk of
chemicals to man. Vol. 7, Some anti-thyroid and related substances,
nitrofurans and industrial chemicals.
Petrova-Vergieva, T. and Ivanova-Chemishanska, L. (1973) Assessment of
the teratogenic activity of dithiocarbamate fungicides. Food Cosmet.
Truhaut, R. et al. (1973) C.R. Acad. Sci. (Paris), CD1276, 229.
Graham, S.L., Hansen, W.H., Davis, K.J. and Carleene, H.P. (1973)
Effects of one-year administration of ethylenethiourea upon the
thyroid of the rat. J. agr. Food Chem., 21:324-329.
Sram, R.J. and Benes, V. (1974) Observations. (Unpublished).