FAO/PL:1967/M/11/1
WHO/Food Add./68.30
1967 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD
THE MONOGRAPHS
The content of this document is the result of the deliberations of the
Joint Meeting of the FAO Working Party of Experts and the WHO Expert
Committee on Pesticide Residues, which met in Rome, 4 - 11 December,
1967. (FAO/WHO, 1968)
FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS
WORLD HEALTH ORGANIZATION
Rome, 1968
FERBAM
This pesticide was evaluated toxicologically by the 1965 Joint Meeting
of the FAO Committee on Pesticides in Agriculture and the WHO Expert
Committee on Pesticide Residue (FAO/WHO, 1965). Additional
toxicological information, together with information for evaluation
for tolerances, is summarized and discussed in the following monograph
addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKES
Short-term studies
Rat. A three-generation reproduction study, with two litters per
generation, was conducted at dietary levels of ferbam of 0 and 250
ppm, using 16 males and 16 females per dose level in each generation.
Test animals were maintained for 3 months post-weaning before the
first matings. No effect on fertility, gestation, viability, lactation
or litter size was seen. No gross or histological abnormalities, as
compared with controls, were found in animals selected for examination
from the second litter of the third filial generation (Sherman & Zepp,
1966).
Comments
Although ferbam was only found, in traces, in tissues of rats and
dogs, storage of metabolites should be investigated as part of the
metabolic studies needed on this class of compounds.
In long-term studies in rats a level of 250 ppm produced no
toxicological effect. The same level was without effect in the
three-generation reproduction study.
From the one-year study in dogs the daily dose of 5 mg/kg body-weight
was without toxicological effect.
The chemical nature of the residues of ferbam in or on the plant has
not been ascertained. Studies are needed on the metabolism of the
dithiocarbamates. While these data are being obtained, a temporary
ADI, is proposed.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat. 250 ppm in the diet, equivalent to 12.5 mg/kg body-weight per
day.
Dog. 5 mg/kg body-weight per day.
Estimate of temporary acceptable daily intake for man
0 - 0.025 mg/kg body-weight (alone or in combination with other
dimethyl-dithiocarbamates.)
This value is based on experiments carried out with ferbam and does
not take account of chemical alterations after application.
Further work required
Studies of the compound in plants to determine the chemical nature of
the residues, followed by appropriate toxicological studies.
Results of the above work should be made available not later than 30
June 1971 after which a re-evaluation of this compound will be made.
The re-evaluation may be made at an earlier meeting should relevant
information become available.
EVALUATION FOR TOLERANCES
USE PATTERN
Pre-harvest treatments
Ferbam is used primarily as a pre-harvest spray to protect a number of
agricultural products from plant pathogens.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Twelve applications of equal parts ziram and ferbam at 2 lb/acre to
celery and allowing 7 days for weathering resulted in a residue of 10
ppm (trimmed) and 4.1 ppm (trimmed and wasted). Snap beans sprayed
with one application at 1 1/2 lb/gal/acre and a 6 day time interval
before sampling resulted in a residue of 3.2 ppm (du Pont, 1961).
Residues Resulting From Supervised Trials
Crop Time interval Treatment Number of Residue Author
days per acre applications ppm
Apples 1 3/4 lbs 1 2.55 du Pont (1957)
14 0.13 "
Grapes 0 2 3 5.3 "
26 2.0 "
Cranberries 74 8 (dust) 2 0.4 "
Apples 63 3 4 4.6 Barry et al, 1957)
RESIDUES IN FOOD AT THE TIME OF CONSUMPTION
A recent survey of five composite basic 2-week diets for males 14-19
years old showed the presence of six dithiocarbamates with values
ranging from 0.4 to 0.8 ppm (Duggan, Barry and Johnson, 1966). No
residues were found in a more recent survey based upon the analyses of
foods prepared for consumption (Duggan and Weatherwax, 1967), possibly
because the residues decomposed rapidly as the foods were being
prepared.
FATE OF RESIDUES
General Considerations
Ferbam is only slightly soluble in water to the extent of 120 ppm.
However, this value may not be reliable as the pH has a pronounced
effect on its solubility (Thorn and Richardson, 1962; Thorn and
Ludwig, 1962) as well as on its conversion to thiuram. When feeding
the sodium salt of dimethyldithiocarbamic acid to plants three new
antifungal compounds were found (Dekhuizen, 1961, 1964) one identified
as a B-glucoside conjugate of dimethyldithiocarbamate (Kaslander,
Sijpesteijn and van der Kerk, 1961), another as the conjugate with
alanine (Kaslander, Sijpesteijn and van der Kerk, 1962) and the third
as yet unidentified.
METHODS OF RESIDUE ANALYSIS
Residues have been determined by releasing either the dimethylamine
(Barr, Clark and Jacks, 1957) or the carbon disulfide (Pease, 1957) on
acid treatment of the sample and measuring the intensity of a coloured
copper complex formed. Since the colour formation is critical an
improved modification has bean outlined (Cullen, 1964). Better
recoveries from a variety of crops have resulted from changes in the
order of the acid decomposition procedure (Gordon, Schuckert and
Bornak, 1967). Methods using polarographic techniques have also been
developed (Nangniot, 1966; Vogeler, 1967).
RECOMMENDATIONS FOR TOLERANCES
Although some progress has been reported, neither the chemical nature
nor the mode of action of the residues of ferbam in or on the plant
have been ascertained and there is no specific method of analysis
available. Accordingly, no tolerance figures can be recommended.
FURTHER WORK
Further work required
Further work is required on the metabolism of ferbam in or on the
plant to include the identification and mode of action of any critical
intermediates, and on the development of specific methods of analysis.
The data on this subject is required prior to 30 June 1971.
NATIONAL TOLERANCES
Country Tolerance, ppm Crop
Canada 7 apples, apricots, asparagus, beans,
(calculated as zineb) beets, blackberries, black-eyed peas,
blueberries, broccoli, Brussels sprouts,
cabbage, carrots, cauliflower, celery,
cherries, collards, corn, cranberries,
cucumbers, currants, dates, eggplants,
gooseberries, grapes, guavas, huckleberries,
kale, kohlrabi, lettuce, loganberries,
mangoes, melons, mustard greens,
nectarines, onions, papayas, peaches,
peanuts, pears, peas, peppers, plums, fresh
prunes, pumpkins, quinces, radishes,
raspberries, rutabagas, spinach,
squash, strawberries, summer squash,
tomatoes, turnips;
U.S.A. 7 apples, apricots, beans, blackberries,
blueberries, broccoli, cabbage, cantaloupe,
carrots, celery, cherries, citrus fruits,
cranberries, cucumbers, gooseberries,
grapes, lettuce, loganberries, peaches,
pears, peppers, plums, potatoes, prunes,
raspberries, squash, strawberries;
0.1 almonds
Germany 1.0 leaf vegetables, fruit vegetables,
pulses, fruit incl. grapes.
REFERENCE PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES
Sherman, H. & Zapp, J. A. (1966) Unpublished report submitted by E.I.
du Pont de Nemours & Co.
REFERENCES PERTINENT TO EVALUATION FOR TOLERANCES
Barr, H.E., Clark, P.J., Jacks, H. (1957) Determination of
tetramethylthiuram disulfide and dimethyldithiocarbamate sprays on
apples. New Zealand J. Sci. Tech. Sect. B,38: 425-532.
Cullen, T.E. (1964) Spectrophotometric determination of
dithiocarbamate residues in food crops. Anal. Chem., 36: 221-224.
Dekhuijzen, H.M. (1961) The transformation in plants of sodium
dimethyldithiocarbamate into other fungitoxic compounds. Nature, 191:
198-199.
Dekhuijzen, H.M. (1964) The systemic action of
dimethyldithiocarbamates on cucumber scab caused by Cladosporium
cucumerinum and the conversion of these compounds by plants. J.Plant
Path. (Netherlands), 70: 1-75.
Duggan, R.E., Barry, H.C., Johnson, L.Y. (1966) Pesticide residues in
total diet samples. Science, 151: 101-104.
Duggan, R.E. Weatherwax, J.R. (1967) Dietary intake of pesticide
chemicals. Science, 157: 1006-1010.
du Pont, E.I. (1957) Submission to Canada Department of Health and
Welfare, Food and Drug Directorate.
du Pont, E.I. (1961) Submission to Canada Department of Health and
Welfare, Food and Drug Directorate.
FAO/WHO. (1965) Evaluation of the toxicity of pesticide residues in
food. FAO Meeting Rept. PL/1965/10/1; WHO/Food Add./27.65.
FDD/Canada. (1967) Food and Drug Directorate, Canada. T.I.L. 290, 15
Sept.
Gordon, C.F., Schuckert, R.J., Bornak. W.E. (1967) Improved method for
the determination of ethylenebisdithiocarbamate residues in plants,
fruits and vegetables. J. Assoc. Off. Anal. Chem. 50: 1102-1108.
Kaslander, J., Kaars Sijpesteijn K., van der Kerk, G.J.M. (1961) On
the transformation of dimethyldithiocarbamate into its ß-glucoside by
plant tissues. Biochim. Biophys. Acta., 52: 396-397.
Kaslander, J., Kaars Sijpesteijn, A., & van der Kerk, G.J.M. (1962) On
the transformation of the fungicide sodium dimethyldithiocarbamate
into its alanine derivative byplant tissues. Biochim. Biophys. Acta,
60: 417-419.
Nangniot, P. (1966) L'application des methodes electrochimiques a
l'etude des residue de pesticides. Mededel. Landbouwhogeschool
Opzoekingstat. Staat Gent, 31: 447-473.
Pease, H.L. (1957) Determination of dithiocarbamate fungicide
residues. J. Assn. Off. Agric. Chem. 40:1113-1118.
Thorn, G.D., Ludwig, R.A. (1962) The dithiocarbamates and related
compounds. Amsterdam, Elsevier Publ. Co., 234 p.
Thorn, G.D., Richardson, L.T. (1962) Ferbam - Some observations.
Mededel. Landbouwhogeschool Opzoekingstat. Staat Gent, 27: 1175-1178
USDA. (1967) Summary of registered agricultural pesticide chemical
uses. 2nd ed. Suppl. III.
Vogeler, von K. (1967) Kolorimetrische und polarographische
bestimmungen von ruckstanden in und auf pflanzen nach anwendung von
Antracol. Pflanzenschutz-Nachrichte Bayer