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
MANEB
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 Residues (FAO/WHO, 1965). Additional
toxicological information, together with information for evaluation
for tolerances, is summarized and discussed in the following monograph
addendum.
IDENTITY
Other relevant chemical properties
Commercial formulations include a wettable concentrate with a minimum
of 70 per cent maneb and a dust containing about 5 per cent maneb.
EVALUATION FOR ACCEPTABLE DAILY INTAKES
Biochemical aspects
Maneb was not stored in the tissues of rats fed up to 2500 ppm for 2
years, or in tissues of dogs given daily doses of up to 75 mg/kg for 1
year (Clayton et al., 1957).
Acute toxicity
LD50 mg/kg
Animal Route body-weight Reference
Rat oral 6750 Clayton et al., 1957
Short-term studies
Rat. Administration of single oral doses of 1500 mg/kg
body-weight/day for 10 days to six male rats caused weight loss,
weakness of hind limbs and one death after eight doses (Clayton et
al., 1957).
Groups of 5 male and 5 female rats were fed 0, 100, 1000 and 10,000
ppm maneb for 90 days. No clinical signs or pathological changes were
found at 1000 ppm in females, or at 100 ppm in males and females.
Higher dose levels caused weight loss, weakness, stiffness of hind
limbs, and 10,000 ppm caused 80 per cent mortality. Thyroid
hyperplasia was seen at 10,000 ppm and, to a lesser extent, in males
at 1000 ppm. The remaining animals appeared normal (Clayton et al.,
1957).
A three-generation reproduction study with two litters per generation,
was done using 16 male and 16 female rats per dose level for each
generation, at 0, 125 and 250 ppm maneb. Test animals were maintained
for 3 months post-weaning before the first matings. No effect was seen
on fertility, gestation, viability, lactation or litter size. No gross
or histological abnormalities, as compared with controls, were found
in animals selected for examination from the third filial generation
(Sherman & Zapp, 1966).
Comments
In long-term studies in the rat a level of 250 ppm was without
toxicological effect. The same level was without effect in the
three-generation reproduction study.
In the one-year study in dogs, the only effect seen at the dose level
of 20 mg/kg daily, was a loss in body-weight in one animal.
The chemical nature of the residues of maneb 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.
Estimate of temporary acceptable daily intake for man
0 - 0.025 mg/kg body-weight (alone or in combination with other
ethylene bis-dithiocarbamates.)
This value is based on experiments carried out with maneb 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
Maneb in primarily used as a pre-harvest spray to protect agricultural
crops, both fruit and plants, from invasion by fungal plant pathogens.
Initially being relatively insoluble, spraying and dusting involves
the whole plant. Residues are reduced by weathering, metabolism by the
plant, and washing and trimming the product. During the weathering and
metabolism by the plant a number of products result, such as ethylene
thiuram monosulfide, ethylenethiuram disulfide and ethylenethiourea.
RESIDUES IN FOOD AT TIME OF CONSUMPTION
A recent survey of 5 composite basic 2-week diets for males, 14 to 19
years, identified 6 dithiocarbamates, including maneb with values
ranging from 0.4 to 0.8 ppm (Duggan, Barry & Johnson, 1966)
FATE OF RESIDUES
General considerations
The manganese salt has a low water solubility and is stable in a dry,
inert atmosphere. However, degradation slowly occurs on exposure to
air and moisture to a variety of compounds. Ethylene thiuram
monosulfide (ETM) and ethylene thiuram disulfide (ETD) (Morehart &
Crossan, 1965) as well aa ethylene thiourea and 2 unidentified
products (Fishbein & Fawkes, 1965) by chromatography. The former
authors suggested from their metabolism studies with fungal spores
that toxicity is due mainly to ETD. However, this is a dynamic system
and possibly the ETM could not be detected. In a modified zineb
preparation, ETM could be detected and its action on rat liver
mitochondria examined (Kovacs & Caumo, 1966).
METHODS OF RESIDUE ANALYSIS
To date the residue is estimated by measuring the carban disulfide
released on acid treatment and recent modifications to suit different
crops are outlined (Gordon, Schuckert & Bornak, 1967). However, the
method is non-specific.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Crop Rate Number Pre-harvest Residue
of of interval (ppm) Reference
application applications (days)
(lb/acre)
almonds 9 - 129 (0.01-0.12) 0.05 (meat) Rohn & Haas (1964)
(12.4-26.4) 20 (husks) "
bananas 2*** post harvest < 0.1 (pulp) "
3.0 (peels) "
4 5 0 13.0* du Pont (1958)
broccoli 4 5 1 4.5** "
4 7 14 1.4 "
celery 1.5 7 7 7.4 "
cherries 6 1 14 (2.9-3.4) 3.3 Rohm & Haas (1964)
chicken
muscle (feed contained 45 ppm) nil "
cranberries 6 4 55 (0.35-0.61) 0.48 "
egg albumen (feed contained 45 ppm) nil "
/yolk
lettuce 2 3 23 25 du Pont (1958)
(stripped)
lima beans 2 5 0 0.04 "
2 5 7 nil "
peaches 2 3 15 8.4 "
RESIDUES RESULTING FROM SUPERVISED TRIALS (cont'd)
Crop Rate Number Pre-harvest Residue
of of interval (ppm) Reference
application applications (days)
(lb/acre)
sugar beet 2.5 2 65 (0.70-1.10) 0.43 Rohm & Haas (1964)
enslage
Residue (ppm)
Trimmed/washed Commercially processed
* 4.0 0.28
** 2.7 <0.25
*** lb/gal.
NATIONAL TOLERANCES
Country Tolerance Crop
Canada 2 ppm bananas (edible pulp)
7 ppm apples, beans (dry), carrots, corn, cranberries, cucumbers,
eggplant, figs, grapes, melons, onions, peppers, pumpkins,
squash, tomatoes, turnips (roots).
10 ppm apricots, beans (fresh), broccoli, Brussels sprouts,
cabbage, cauliflower, celery, Chinese cabbage, collards,
endive, kale, kohlrabi, lettuce, mustard greens,
nectarines, peaches, rhubarb, spinach and turnip tops.
USA essentially the same as for Canada except potatoes
(0.1 ppm) and sugar beet tops 45 ppm (not to be applied
within 10 days of harvest and tops not to be fed to
livestock).
West Germany 3 ppm leafy vegetables, fruit, pulses.
RECOMMENDATIONS FOR TOLERANCES
Although some progress has been reported neither the chemical nature
nor the mode of action of the residues of maneb 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 maneb 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 to required prior to 30 June 1971.
REFERENCES PERTINENT TO EVALUATION FOR ACCEPTABLE DAILY INTAKES
Clayton, J.W., Hood, D.R., Barnes, J.R. & Borgmann, A.R. (1957)
Unpublished report submitted by E.I. du Pont de Nemours & Co.
Sherman, H. & Zapp, J.A. (1966) Unpublished report submitted by E.I.
du Pont de Nemours and Co.
REFERENCES PERTINENT TO EVALUATION FOR TOLERANCES
Duggan, R.E., Barry, H.C., & Johnson, L.Y. (1966) Pesticide residues
in total diet samples. Science, 151: 101-104.
du Pont, E.I. (1958) Submission to Canada Dept. of Health and Welfare,
Food and Drug Directorate.
FAO/WHO (1966) Evaluation of the toxicity of pesticide residues in
food. FAO Meeting Rpt. PL.1965/10/1; WHO Add./27.65.
Fischbein, L., & Fawkes, J. (1965) Thin layer chromatography of
metallic derivatives of ethylenebis (dithiocarbamic acid) and their
degradation products. J. Chromatog., 19: 364-369.
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.
Kovacs, A., & Caumo, B. (1966) Systemicity of zinc
ethylenebisdithiocarbamate. Atti. Simp. Int. Agrochim., 6: 263-269
(1967, Chem. Abstr. 67: 90012 r).
Morehart, A.L., & Crossan, D.F. (1965) Studies on the ethylenebis
dithiocarbamate fungicides. Exp. Stn. Bull. 357, Agric. Exp. Stn.
Univ. Delaware, Newark, Del. 26 p.
Rohm and Haas. (1964) Submission to Canada Dept. of Health and
Welfare, Food and Drug Directorate.