PROPINEB JMPR 1977
IDENTITY
Chemical name
zinc propylenebisdithiocarbamate
Synonyms
(R) Antracol
Methylzineb
Mezineb
LH 30/Z
Bay 46 131
Structural formula
S S
| |
(-Zn-S-C-NH-CH2-CH-NH-C-S-)X
|
CH3
Empirical formula
(C5H8N2Zn)X
Other information on identity and properties
Composition Satisfactory information was available to the
Meeting
Appearance White to yellowish powdery practically odourless
Molecular Weight 289.8 (for the theoretical monomeric compound)
Melting point The technical product undergoes degradation,
accompanied by brown discoloration, above about
160°C; at about 300°C, the organic components of
the product sublime, leaving a very small
inorganic remainder of ZnS.
Solubility Practically insoluble in all usual solvents
Stability Unstable in strongly alkaline and strongly acid
conditions
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Propineb, a propylene analogue of zineb, has moderate acute toxicity.
It degrades to propylene thicurea (PTU).
Orally administered propineb is readily excreted via urine and faeces.
Propineb has a goitrogenic effect. Following oral administration, high
tissue concentration in, and enlargement of the thyroid and pituitary
glande occurred. These effects are reversible.
A dominant lethal test in mice was negative. Reproduction studies in
rats show no adverse effect at 20 and 60 ppm, but muscular damage
(myasthenia) and reduced fertility occurred at 200 ppm. In a
teratogenicity study, a teratogenic effect was produced only at a dose
which was highly toxic and lethal to the dams. In a long-term study, a
significent increase in the incidence of thyroid benign tumours and
skeletal muscle degeneration was observed at dietary level of 1000 ppm
and above. Significant thyroid enlargement occurred in the males at
dietary levels of 100 ppm and above. In another two-year feeding
experiment with rats at a level of 100 ppm, serum protein-bound iodine
(PBI) was lowered.
Two studies in dog were carried out (four months and two years). No
adverse effects were seen at 3000 ppm. In a study with rats for two
years, a dose-dependent reduction of growth and significant increase
in liver and kidney weights were noted at 100 ppm and above.
In a four-week study with hens, no effects were seen at 1000 ppm and a
dose-dependent increase in thyroid weight occurred at 2000-8000 ppm.
No neurotoxicity was observed.
Because of the concern of the Meeting regarding the potential for
thyrotoxicity and tumorigenicity of PTU (known to occur with ETU), the
Meeting recommended a temporary ADI for humans.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 10 mg/kg in the diet, equivalent to 0.5 mg/kg bw
Dog: 3000 mg/kg In the diet, equivalent to 75 mg/kg bw
ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR HUMANS
0-0.005 mg/kg bw
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERN
Propineb is a propylenebisclithiocarbamate fungicide notable for its
rapidity of action and its long-lasting activity. It has a broad
spectrum of activity and is especially used as a protective treatment
for the control of numerous fungal disease pathogens belonging to the
classes and groups of Oomyoetes, Ascomycetes, Basidiomycetes and Fungi
imperfecti. Propineb is marketed in more than 70 countries and hence
is used worldwide.
TABLE 1. Application rates of propineb on various crops
Application rate
Recommended
Number of pre-harvest
Crop Formulation (in kg a.i./ha) applications interval (days)
Bananas WP 1.4 - 2.1 6 - 14 7
Pome fruit
(apples, pears) WP 1.4 - 2.8 8 - 12 7 - 10
Cherries WP 1.4 - 2.8 2 - 3 7
Plums, damsons WP 1.4 - 2.8 2 - 5 7
Peaches WP 1.4 - 2.8 2 - 3 7 - 10
Currants(fresh) WP 2.1 - 2.8 2 - 3 14
Gooseberries WP 2.1 - 2.8 2 - 3 14
Citrus fruit WP 2.1 - 4.2 3 - 6 14
Grapes WP 1.75 - 2.8 4 - 10 21 - 28
DP 1.4 6 - 8 21 - 28
Beans WP 1.0 - 2.1 3 - 5 7
Cucurbits WP 0.84 -1.4 2 - 4 4 - 7
Celery WP 0.84 -1.4 2 - 4 7 - 14
Tomatoes WP 0.84 -1.75 4 - 8 4
Onions WP 1.4 - 2.1 2 - 3 7 - 10
Potatoes WP 1.05 - 2.8 4 - 8 7
Cereals WP 1.4 - 2.1 1 - 3 28 - 35
Rice WP 1.4 - 2.1 1 - 3 21
Groundnuts WP 1.4 - 2.1 4 - 6 14
Coffee WP 2.3 4 4 - 7
Tobacco WP 2.1 - 2.8 10 - 16 7
DP 3.0 - 4.0 10 - 16 7
Hops WP 1.5 - 5.6 10 - 16 7
Post-harvest treatments
Dose Number of
Crop Formulation (in g. a.i./ha) applications
Currants (fresh) WP 2.1 -2.4 2
WP= Wettable powder
DP= Dust
TABLE 2. Residues of propineb in crops after application of 70% WP formulation (Supervised Trials: Bayer, 1977)
Application rate No. of Days after Residue (mg/kg)
Crop kg/ha applications application range mean
Apples 2.1 12 0 n.d. - 5.4 (3) 3.2
4 1.5 - 2.7 (3) 2.2
7 1.7 - 2.4 (3) 2.0
10 1.1 - 2.2 (3) 1.5
14 0.9 - 2.3 (3) 1.6
Bananas 2.35 - 3.53 4 1 n.d. (6) n.d.
Pulp 3 n.d. (6) n.d.
7 n.d. (6) n.d
14 n.d. (6) n.d
21 n.d. (6) n.d.
Peel 1 n.d. - 0.5 (6) 0.2
3 n.d. - 0.4 (6) <0.2
7 n.d. - 0.55 (6) 0.2
14 n.d. - 1.35 (6) 0.3
21 n.d. - 0.35 (6) <0.2
Total 1) 2.1 - 3.15 12 0 - 3 n.d.- <0.2 (20) <0.2
7 n.d.- <0.2 (6) <0.2
12 n.d.- <0.2 (3) <0.2
Beans 1.05 2 - 3 0 0.9 - 1.0 (2) 1.0
3 0.2 - 0.8 (2) 0.5
7 n.d. - 0.3 (3) 0.1
14 n.d. (3) n.d
21 n.d. (3) n.d.
Celeriac 1.05 2 - 4 0 n.d. (3) n.d
Edible root 14 n.d. - 0.2 (6) <0.1
21 n.d. (6) n.d
28 n.d. (3) n.d
35 n.d. (3) n.d
TABLE 2. (Continued)
Application rate No. of Days after Residue (mg/kg)
Crop kg/ha applications application range mean
Celeriac 1.05 2 - 4 0 16.5 - 25.7 (3) 21.7
leaf 14 0.2 - 0.4 (3) 0.3
21 0.2 - 0.3 (3) 0.2
28 0.1 - 0.3 (3) 0.1
35 n.d. - 0.2 (3) <0.1
Cherries 2.8 3 0 2.2 - 14.0 (5) 7.4
7 0.6 - 2.3 (5) 1.7
14 0.2 - 0.5 (5) 0.3
21 0.1 - 0.3 (5) 0.2
28 n.d. -<0.1 (3) <0.1
Citrus 2.52 -4.2 2 - 4 78/79 0.08- 0.17 (2) 0.13
(Satsuma Orange) 124/228 0.07 (2) 0.07
Pulp
Peel 78/79 0.09-0.18 (2) 0.14
124/128 0.06-0.31 (2) 0.19
Juice 78/79 < 0.05 (1) 0.05
Coffee 21 g/shrub 4 6 n.d. (1) n.d.
(beans, hulled)
Cucumber 1.4 3 7 n.d. (1) n.d.
6X 0.1
g/plant 6 3 n.d. - <0.3 (2) n.d.
Blackcurrants 2.8 2 - 3 0 11.8 - 38.6 (3) 25.2
7 4.35 - 17.4 (4) 11.7
11-14 1.2 - 13.4 (6) 8.7
21 0.65 -10.3 (5) 6.3
28 0.25-10.7 (5) 5.0
38-39 0.4 - 1.1 (2) 0.75
TABLE 2. (Continued)
Application rate No. of Days after Residue (mg/kg)
Crop kg/ha applications application range mean
Red currants 2.8 2 - 3 0 7.2 - 34.2 (3) 20.8
7 2.15 - 22.6 (4) 10.2
11-14 1.9 - 16.4 (10) 6.3
21 0.4 - 9.9 (7) 3.8
28 0.3 - 7.6 (7) 3.5
39 0.3 - 1.2 (2) 0.75
Grapes 2.1 - 3.5 6 - 10 0 4.3 - 25.45 (9) 15.2
14/15 2.05 -11.2 (9) 7.6
28 0.95 -8.2 (9) 5.0
35 0.6 - 5.3 (7) 3.1
42-78 n.d. - 6.15 (15) 3.2
Hops 1.5 - 5.6 9 - 20 0 - 6 76.5 - 475 (3) 253
7 - 9 86 - 309 (4) 175
14 14 (1) 14
Sweet melon
Pulp 1.4 3 7 n.d. (1) n.d.
Peel 7 0.2 (1) 0.2
Onions 2.52 10 - 14 7 0.03 (2) <0.03
7 - 13 12 0.03 - 0.06 (2) 0.05
7 - 13 20 0.03 (2) 0.03
Peaches 2.1 - 2.8 3 0 2.45 - 30.5 (3) 16.9
4 - 7 0.2 - 9.9 (4) 4.9
14 0.4 - 3.8 (3) 2.4
21 1.3 (2) 1.3
28 0.85 - 5.0 (2) 2.9
Plums 2.8 3 0 1.0 - 1.4 (3) 1.2
7 1.0 - 1.8 (3) 1.3
14 0.65 - 0.7 (3) 0.7
21 0.35 - 0.55 (3) 0.4
28 0.25 - 0.4 (3) 0.3
TABLE 2. (Continued)
Application rate No. of Days after Residue (mg/kg)
Crop kg/ha applications application range mean
Potatoes 1.26 6 7 n.d. (3) n.d.
22 n.d. (1) n.d.
51-60 n.d. (2) n.d.
Tobacco 0.2 - 0.4 7 - 17 2 - 7 90 - ca.4000 (28) 625
1.3 - 4.6 11 - 18 3 - 5 64.9 - 465 (3) 224
12 45.4 (1) 45.4
17 158.5 (1) 158.5
Tomatoes 1.4 6 0 0.2 - 0.55 (3) 0.5
Greenhouse 3 0.3 - 0.65 (3) 0.5
4 0.4 - 0.8 (3) 0.6
7 0.3 - 0.75 (3) 0.45
Field-grown 1.75 5 0/1 2.2 - 3.35 (2) 2.8
3 1.65 - 2.3 (2) 2.0
7 0.4 - 1.8 (2) 1.1
Wheat 1.575 - 2.1 1 - 4 0 37.5 - 53.0 (3) 43.3
Ears 7 7.15 - 10.35 (3) 8.45
Grains 26 0.3 (1) 0.3
38-42 n.d. - 0.15 (6) 0.1
47-68 n.d. - 0.5 (9) 0.1
Straw 42-68 0.85 - 1.6 (6) 1.1
1) The peel was analyzed, and the residue found was converted to whole fruit.
Pre-harvest treatments
Propineb is formulated as a wettable powder and as a dust, with the
wettable powder formulation being used predominantly. The major uses
of propineb are in viticulture, fruit-growing and vegetable-growing.
It is used also on a wide range of other crops including tobacco,
hops, rice, groundnuts and coffee. The application rates for the
different crops are listed in Table 1. The large variation in the
numbers of applications per season is accounted for not only by the
many different diseases on each crop but also by the very large
differences in infection conditions from one region to another and
also from year to year.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Data on residues of propineb (determined as evolved CS but expressed
as propineb) in various crops following supervised treatments with the
wettable powder are shown in Table 2. The figures in brackets
represent the number of analytical results reported (Bayer, 1977).
Other uses
Propineb is also recommended for use on ornamentals (WP formulation).
FATE OF RESIDUES
In plants
The distribution and metabolism of (14C) propineb was studied on
apples and grapes after a single application in 1972/73 (Vogeler et
al., 1977a), and on grapes after three applications in 1976 (Vogeler
et al., 1977b), under field conditions.
Degradation of (14C) propylenethiourea (PTU) on apples was also
studied (Vogeler et al., 1977a). The studies were model experiments
under field conditions to investigate metabolism and not designed to
make quantitative determinations of metabolite residues after
commercial application of propineb.
Whereas propineb remains mainly on the fruit surface, some of the
metabolites formed can penetrate, at least partially, into the pulp.
Degradation of propineb results in the formation of a metabolite which
has not yet been identified, and also the following known metabolites:
propyleneurea (PU), PTU, 4-methylimidazoline, and the methyl compounds
of DIDT (5,6-dihydro-3H-imidazo (2,1-C)-1,2,4-dithiyole-3-thione) and
Jaffé's base (3-(2imidazolin-2-yl)-2-imidazolidinethione. In the 1976
study involving three applications to grapes, the metabolites were
found to be present in the grapes in the following percentages at
harvest:
Methyl
Propineb 4-methyl- Unidentified compound PU PTU Methyl
imidazoline metabolite of Jaffé's compound
base of DIDT
41 1.7 7 4.6 4.3 9 9
In the studies conducted in 1972-73, the unidentified metabolite
occurred in a larger amount than in the 1976 study. The methyl
compounds of DIDT and Jaffé's base were detected only in the 1976
study. 4-methylimidazoline is formed in the isolation step as a result
of a transformation of the unidentified metabolite, which is not
stable as a free base. It is presumed that this compound is also
formed from this metabolite in the plant.
Degradation of PTU on apples proceeds rapidly and as it results in the
formation of the same unidentified metabolitel it is assumed that
propineb is degraded mainly via PTU. The residue level of PTO is
governed mainly by the formation of PTU from propineb and the further
degradation of PTU.
In soil
In field studies, propineb was found to undergo relatively fast
degradation with half-lives in the range 2-8 clays, while in similar
studies conducted in Japan, a halflife of about 20 days was recorded
after five applications (Bayer, 1977). The half-lives in laboratory
degradation studies were 1 and 9 days while under experimental
conditions in Japan they were less than 1 day (Bayer, 1977).
In leaching studies conducted with propineb in which 200 mm of water
(simulating rainfall) vas passed through 300 mm-high soil columns in 2
days no propineb was found in the leachate (Bayer, 1977).
In metabolic studies conducted with (14C) propineb in two standard
soils it was degraded to PU to the extent of more than 50% of the
amount applied (Vogeler, 1976). In addition, formation of CO2 was
noted. Small amounts (about 4%) of PTU were found. Other metabolites
occurred only 2 in amounts equivalent to less than 4% of the applied
propineb; they were not identified.
Degradation of (14C) PTU also resulted in the formation mainly of PU
and CO2. At the end of the study period, PTU was no lonjer
detectable. Pr)m the comparison of-the results of the degradation
studies with propineb mid PTU, it is concluded that degradation of
propineb proceeds mainly via PTU.
The behaviour of (14C) propineb in field lysimeters with cores of
undisturbed soil was studied over a period of 22 months by
Mittelstaedt and Führ (1977). The total radioactivity showed a loss of
43% in follow soil with no plant cover and a loss of 26% in soil
covered with grass. This loss may be attributed largely to the
degradation of propineb CO2, because laboratory studies revealed that
39% of the applied propineb was degraded to C02 after 74 days. The
radioactivity still present in the field soil after 22 months was
retained largely in the upper 5 cm layer. Of this radioactivity, only
about 10% was extractable. Heavy absorption or incorporation in the
organic matter of the soil probably prevented further translocation or
leaching. Of the radioactivity originally applied, 1.8% was recovered
in the leachate of the soil with no plant cover and 0.3% was recovered
in that of the covered soil. From the results of an additional
laboratory study (Vogeler, 1977), it is assumed that the radioactivity
in the leachates was accounted for by PU and other polar compounds.
METHODS OF RESIDUE ANALYSIS
Propineb residues can be determined by the well-known CS2 evoluation
methods such as that on Keppel (1969), in which stannous chloride used
as a reducing agent.
A modified procedure based on the Keppel method has recently been
proposed (Thier, 1977).
Propylene thiourea can be determined by gas chromatography, without
derivatization, by an adaptation of the method of Otto et al. (1977).
The sample is extracted with methanol and the methanol evaporated. The
remaining water phase is shaken out with n-hexane and cleaned up on an
aluminium oxide column. The aqueous eluate is concentrated and shaken
out with dichloromethane. After evaporation of the dichloromethane,
the residue is dissolved in methanol and PTU directly determined by
gas chromatography.
NATIONAL TOLERANCES REPORTED TO THE MEETING
The following national tolerance and pre-harvest intervals were
reported to the Meeting.
Country Crop Tolerance, Pre-harvest
mg/kg interval
days
Australia General 3
Austria General 14
Vegetables,
fruit crops 2.0 (dithiocarbamates
calculated totally
Other crops 0.05 as carbon
disulphide)
Belgium Cereals 0.2 calculated as CS2
Fruit, vegetables,
excl. potatoes and
citrus 2.0 as CS2
Potatoes 0.5 as CS2
Field-grown:
Grapes, hops 42
Leek, onions
celery, asparagus - 28
shallot, beans,
cereals, spinach
Gherkins 10
All other crops 14
Field-grown and
under glass:
Lettuce, endive from 1.3 - 1.11 28
Under glass:
Lettuce, endive from 1.11 - 1.3 42
Radish, spinach 28
Tomatoes, gherkins,
cucumbers 3
Country Crop Tolerance, Pre-harvest
mg/kg interval
days
German
Democratic
Republic (GDR) Field crops -
Potatoes 7
Top fruit and
vegetables 10
Small fruit, leafy
vegetables 21
Fruit-producing
vegetables 4
Grapes 14
Crops for production
of baby
foods and dietary
foods 28
Crops for production
of drugs 21
Forage crops,
grassland (pastures) 7
Pome fruit, small
fruit, strawberries,
stone fruit, nut
crops, root
vegetables,
leafy vegetables, 3.0 calculated as
brassicas, legumes carbon disulphide
(pulse crops),
fruit-producing
vegetables
Citrus fruit,
cereals,
milled grain
products,
potatoes, onions,
vegetable and
animal fats, 0.1 calculated as
meat, fish, eggs, carbon disulphide,
milk, baby foods
Country Crop Tolerance, Pre-harvest
mg/kg interval
days
Germany Federal
Republic of (FRG) Potatoes 7
Pome fruit 10
Stone fruit, small
fruit 21
Grapes 42
Tomatoes
(field-grown
and under glass) 4
Celery 28
Hops, tobacco 7
Vegetables, excl.
cucumbers
and tomatoes 2.0 dithiocarbamates,
Fruit crops 2.0 thiuram disulphides
Cucumbers and
tomatoes 1.0 calculated totally
Other food crops 0.05 as carbon disulphide
Hungary General 3.0
Tomatoes (processing) 8
Peppers (processing) 10
Fruit crops and grapes 30
All other crops 21
Israel General unrestricted
Italy General 7
Mexico Avocado, cocoa, lemons,
mandarin oranges,
bergamot oranges, 7
mango, apples, pears,
potatoes
Netherlands Potatoes, cereals 0.5 as CS2
All other crops 2.0 as CS2
New Zealand General 7
Country Crop Tolerance, Pre-harvest
mg/kg interval
days
Norway General 14
Portugal General 7
South Africa General 3.0
Wine grapes 28
Table grapes 28-42
Tomatoes, potatoes 3
Boysenberries,
youngberries 14
Spain General 10
Sweden General 30
Switzerland Grapes 3.0 21
Vegetables,
excl. lettuce 21
Yugoslavia Tobacco 7*
Grapes 42*
All other crops 14*
* (official recommendation)
APPRAISAL
Propineb is a broad specturm propylenebisdithiocarbamate fungicide
which is marketed world-wide. Major uses are pre-harvest treatments of
fruits and vegetables and in viticulture. The wide variation in
application frequency (1 to 16 applications) is due to the different
natures and extent of the fungi against which it is aimed.
Residues data were provided from supervised trials of propineb
applications to a range of crops. Residues observed, expressed as
propineb, varied from up to 10 mg/kg on grapes and blackcurrants to
less than 0.05 mg/kg (limit of determination) in banana pulp.
The distribution and metabolism of propineb residues in apples and
grapes have been studied, together with the associated
propylenethiorurea (PTU) in apples. Whereas the parent propineb and
PTU remain mainly on the surface, some other metabolites (of which
several are described) can penetrate at least partially into the flesh
of the fruit. PTO degrades rapidly to yield the same metabolites (some
as yet unidentified) as does propineb, suggesting that the degradation
of propineb may proceed via PTU.
Field studies of propineb degradation in soil have shown half-lives
ranging from 2 to 20 days depending on conditions. Over 50% was
converted to propyleneurea (PU) during similar studies using
0-14 labelled propineb or PTU.
Residue analysis is carried out by CS evolution procedures based on
that of Keppel (1969). A gas-chromatographic method for ETU (Otto et
al., 1977) has been adapted for the determination of PTU residues.
RECOMMENDATIONS
As the analytical method depends on CS2 evoluation, temporary maximum
residue limits identical to those of the other dithiocarbamates are
recommended (see "Dithiocarbamate fungicides"). The limits are for
CS2.
FURTHER WORK OR INFORMATION
REQUIRED (by July 1980)
1. A study of the mechanism of action of propineb on the thyroid.
2. Further work to elucidate the mode of action of PTU and its
long-lerm toxicity.
3. Information regarding the fate of residues during food
processing, including cooking.
REFERENCES
Bayer, (1971) Data submitted by Bayer AG (unpublished).
Keppel G.E. (1969) Modification of the Carbon Disulfide evolution
Method for Dithiooarbamate Residues. J. Ass. Off. Anal. Chem. 52,
162-167.
Mittelstaedt, W. and Führ, F. (1977) Verhalten von Propineb in
bewachsenem und unbewachsenem Boden. Landwirtroh. Forsoh., in press.
Otto, S., Keller, W. and Drescher, N. (1977) A new gas chromatographic
determination of ethylenethiourea residuee. J. Environ, So. Hlth., B
12 (3): 179-191.
Thier, H.P. (1977) Veröffentlichungen aus den Arbeitsgruppen sur
RUckstandsanalytik der Pestizide in Lebensmitteln. 5. Mitteilung:
Nalytik von DithiocarbamatRückstäden. Lebensmittelchem. gerichtl.
Chem. 3-1, 25-27.
Vogeler, K. (1976) Zum Metabolismus von Propineb, Zineby
Propylenthioharnstoff und Athylenthioharnstoff im Boden nach
BBA-Plerkblatt Nr. 36. Bayer AG, Pflanzenschutz-Anwendungstechnik,
unpublished report RA 726, September, 1976.
Vogeler, K. (1977) Leachine-Laborversuche mit (140) Propineb Bayer AG;
Pflanzenschutz-Anwendunstechnik, unpublished report RA-573, July 20,
1977.
Vogeler K., Drezer Ph., Papp, R.l Steffan, E., Ullerneyer, H.
Verteilung und Metabolismum von Propineb in Apfeln und Weintrauben
sowie der Abbauprodukte Propylenthioharnstoff und Athylenthioharnstoff
in Apfeln. Pflanzenschutz-Nachrichten Bayer 30, 72-97.
Vogeler K., Rapp, A., Steffan, H., Ullemeyer, H. Der Metabolismus von
Propineb in Weintrauben nach dreimaliger Applikation von. Antracol im
Freiland. Bayer AG, Pflanzenschutz-Anwendungstechnik, unpublished
report RA-363, April 28, 1977b.