LEPTOPHOS JMPR 1974
IDENTITY
Leptophos is a draft ISO common name.
Chemical name
O-(4-bromo-2,5-dichlorophenyl) O-methyl phenylphosphonothioate
Synonyms
O-(4-bromo-2,5-dichlorophenyl) O-methyl phenylthiophosphonate
phosvel(R)
Structural formula
Empirical formula
C13H10Br Cl2 O2 PS
Other information on identity and properties
a. Composition of technical leptophos
The technical material as manufactured contains a minimum of 85%
leptophos and about 15% related materials. Its composition is as
shown in Table 1.
TABLE 1. Composition Of technical leptophos
Compound Specification Typical Sample
leptophos 85% min. 87%
O,O-dimethyl phenylphos-phonothioate 8% max. 3.5%
4-bromo-2,5-dichlorophenol 1% max. <0.1%
O,O-bis-(4-bromo-2,5-dichlorophenyl)
phenylphosphonothioate 8% max. 4%
Volatile materials 2% max. 0.5%
Miscellaneous related
compounds approx. 5% total
(A number of unidentified impurities at levels of less than 1% each,
either present at these levels in the starting materials or resulting
from reactions of these materials at a later stage. Halogenated
dibenzo-p-dioxins are absent [limit of detection 0.1 ppm] [Velsicol,
1971a])
b. Physical and chemical properties of leptophos
physical state: white crystals
molecular weight: 411.8
melting point: 70.2 - 70.6°C (99.4% purity)
specific gravity: D 25 = 1.53
4
solubility (g/100 ml solvent at 25°C):
water practically insoluble in water
(0.03 mg/l)
benzene 133
xylene 73
acetone 62
cyclohexane 14
heptane 7
isopropyl alcohol 2.4
stability:
thermal stable at normal temperatures; at 180°C
85% of the material is decomposed in 5
hours, at 208°C in 2 hours.
The main product of thermal decomposition
is the S-methyl isomer
[O-(4-bromo-2,5-ichlorophenyl) S-methyl
phenylphospho-nothioate] [Schwemmer,
1971a].
acids and bases leptophos is hydrolysed slowly under
alkaline conditions at normal
temperatures; the material is stable in
acid conditions.
UV light In the laboratory, when irradiated with
high intensity UV light in the presence of
a strong UV sensitizer, leptophos is
rapidly converted first to
O-(2,5-dichlorophenyl)
O-methylphenyl-phosphonothioate, referred
to as the dichloro-photoproduct, and then
to a material with the empirical formula
C13H10 Cl O2 PS (tentatively identified
as 3-chloro-6-methoxydibenz [c, e]
[1,2]-oxaphosphorin-6-thione or
O-methyl-O, P-(4-chloro
biphenyl-2,6'ylene) phosphonothioate and
referred to as the monochloro-photoproduct
[Schwemmer, 1971b]
UV light increases the rate of hydrolysis,
under field conditions (see "Fate of
residues in water")
c. Formulations
Leptophos is used as EC, wettable powder, dust and ULV
formulations.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Insufficient information was available to the Meeting to evaluate
the compound toxicologically. A preliminary discussion of some aspects
of its toxicology appears in the Report of the Meeting (FAO/WHO, 1975)
and a fuller evaluation at the next Meeting is proposed.
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERN
Leptophos is an organophosphorus insecticide with no appreciable
systemic action. The material is used especially against lepidopterous
larvae, but is also effective against a relatively broad spectrum of
insects including beetles and their larvae, aphids, jassids and
thrips, on various field crops, vegetables and fruits. Particularly
important uses are on cereal crops (including maize and rice), cotton,
sugar-cane, sugar-beet, brassicas, lettuce, tomatoes, potatoes,
tobacco etc. (see registered and recommended uses below). Leptophos is
used in about 25 countries in North-, Central- and South-America,
Asia, Australia and Europe. The compound is applied as a soil-, seed-,
and foliar treatment. Leptophos is not recommended for post-harvest
treatments, or for use on or near livestock.
Pre-harvest treatments
Leptophos is generally used at dosage rates of 0.35 - 1.5 kg
a.i./ha.
The officially registered and/or recommended uses are summarized
in Table 2, with some typical application rates, safety intervals and
limitations.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Residues in crops
Residue data are available from trials, mainly in the USA, on
various vegetables and field crops: brassicas (broccoli, Brussels
sprouts, cabbage); lettuce, potatoes; tomatoes; cotton and cotton
products; maize (field corn and sweet corn). Data on residues in
products of animal origin, e.g. residues in milk and meat of dairy
cattle, meat of chicken and eggs, resulting from the consumption of
residues in feed are also available.
The data from supervised trials on crops are summarized in Table
3. Residues of leptophos and its three main metabolites, the oxygen
analogue, the phenol and desbromo-leptophos were usually determined
separately. In the Table, in order to avoid excessive length, the
leptophos residue is given together with an indication of the nature
and total content of the determined metabolites. Where a metabolite is
not recorded as having been determined its residues were usually
undetectable. In most cases the limit of detection was 0.01 mg/kg. The
results are not generally corrected for apparent residues in untreated
controls.
TABLE 2. Registered or recommended uses of leptophos
Safety
Type of Dosage rate interval
Country Crop application* kg a.i./ha (days) Limitations
Canada Cabbage young plants 50
Carrots, celery, onions, rutabagas,
barley, oats, wheat young plants 60 not on green
bunching onions
Cucumbers, peppers soil 50
Tomatoes soil 70
Potatoes soil 88
Potatoes foliar 21
Head lettuce young plants 28
Sugar beet, sunflower young plants 100
Rape young plants 16
Dominican Rep. Tomato foliar 0.5-1.5 5
and other
Caribbean Broccoli, cabbage, lettuce, potatoes foliar 0.5-1.5 7
countries
Cotton foliar 1.2 10-14
Sweet corn (fresh market) foliar 0.9-1.35 3 when tassels first
emerge, do not feed
treated fodder to
livestock
TABLE 2. (Cont'd.)
Safety
Type of Dosage rate interval
Country Crop application* kg a.i./ha (days) Limitations
Citrus foliar 0.5 not on fruit-bearing
trees
Sugar-cane foliar 0.5-1.5
Tobacco foliar 0.5-1.1 10-14
Japan and Azuki bean, cabbage and chinese
Korea cabbage, rice foliar 0.23-0.34
Sugar-cane foliar 0.17-0.34
Tobacco foliar 0.34
Mexico Beans, soybeans, other vegetables,
alfalfa, cotton, rice, sugar-cane,
citrus fruit, grapes foliar 0.5-1.5
Philippines Rice foliar 1-1.5
Maize, oil palm, tobacco foliar 0.34-0.7
Vegetables foliar 0.34-0.6
USA Broccoli, cabbage, russels sprouts,
tomatoes, maize foliar 0.9-1.35 7 do not apply to corn
or sweet corn which
Lettuce foliar 0.9 7 is to be used for
silage or will be
Cotton foliar 0.9-1.35 28 fed to livestock
Sweet corn (canning and fresh market) foliar 0.9-1.35 3
TABLE 2. (Cont'd.)
Safety
Type of Dosage rate interval
Country Crop application* kg a.i./ha (days) Limitations
Citrus fruit foliar 1.25 g/100 1 only on trees that
will not bear fruit
within a month
Potatoes foliar 0.9-1.35 21
Venezuela Black beans, soybean, cabbage,
cauliflower, lettuce, onions,
potatoes foliar 0.9-1.25 10
* Type of application: young plants = spraying or dusting the crops at an early stage
foliar = spraying or dusting aerial parts at a later stage of development
The numbers used to identify the oxon (II), phenol (V) and
desbromo-leptophos (VI) correspond to those in the metabolic scheme
shown in the section "Fate of residues (Figure 1).
General comments on Table 3.
The main residue component in vegetables and grain crops is the
parent compound leptophos which comprises 82.8 to 95.4% of the total
residue detectable in any samples analysed. The other components of
the residue, the oxygen analogue, the phenol and desbromo-leptophos,
occur in varying proportions. The ratio of metabolites to parent
compound increases with time and the main metabolite is usually the
phenol or apparently the oxon. In a relatively large number of trials,
however, the major part (and sometimes all) of the apparent "oxon
residue" is likely to be an artifact derived from the analytical
equipment. This interfering material was shown to be
bis - (2-ethylhexyl) phthalate.
In root crops such as potatoes, in which the insecticide does not
come in direct contact with the edible parts, the primary residue
component is the phenol hydrolysis product. In corn grain only
leptophos is detected. There is some doubt as to whether this residue
is genuine or caused by contamination from the husks during their
removal.
Broccoli
The half-life of the residues on broccoli is about 3-6 days.
After observing a pre-harvest interval of 7 days the residues were
about 4-5 mg/kg when treatment was at the usual rate (0.9-1.35 kg/ha).
After 14 days the residues were well below 0.5 mg/kg in the single
trial reported.
Cabbage
After application of leptophos at normal rates the maximum
residue after a 7 days pre-harvest interval was about 3.5 mg/kg, after
14 days well below 1 mg/kg.
Lettuce
Removal of the wrapper leaves significantly reduces residues on
lettuce. The lettuce samples which were analysed with the wrapper
leaves on only one sample, taken 7 days after the last application,
had residues which exceeded 5 mg/kg.
Potatoes
When leptophos was applied at the recommended rate of 0.9-1.35 kg
a.i./ha and after observing the recommended pre-harvest period of
three weeks the total residues at harvest were about 0.1 mg/kg or
lower.
Tomatoes
When application was made at the recommended rate of 0.9-1.35 kg
a.i./ha, and after a pre-harvest interval of 5-8 days, residues ranged
from about 0.3 to 3 mg/kg. Only one sample exceeded 2 mg/kg, and in
eight of the twelve the residues were below 1 mg/kg.
Cotton
The residues of leptophos and its metabolites in cottonseed after
the application of leptophos to cotton at normal rates (0.9-1.35 kg
a.i./ha) and a pre-harvest interval of 28 days were below 0.2 mg/kg in
four of the five trials reported. The residues in crude and processed
cottonseed oil are discussed in the section "Fate of residues in
storage and processing."
Corn
After observing a pre-harvest interval of 7 days for field corn
and 3 days for sweet corn, the residues in the ears or kernels varied
between < 0.01 (limit of detection) and 0.05 mg/kg.
Application to field corn which is to be used for silage or when
forage or fodder will be fed to livestock is not permitted, nor is the
feeding of treated sweet corn forage or fodder. Residues in canning
wastes (cobs and husks) varied between 4 and 12 mg/kg; residues in
stalk and leaf of field and sweet corn between 9 and 82 mg/kg. Such
commodities are often used as animal feed. The cob and grain of sweet
corn for table uses contained residues of <0.01-0.16 mg/kg, usually
at or below 0.05 mg/kg. It is to be noted that in several trials
leptophos was applied at normal dosage rates but many times and at
intervals of only two or three days. Lower residues in stalks and
leaves may be expected after less frequent applications and/or longer
intervals.
Residues in products of animal origin
Leptophos is not used on or near animals. Any residues in milk,
meat or eggs occurring as a result of recommended uses of leptophos
could only arise from residues in raw agricultural commodities used as
feed. The data summarized below provide a basis for estimating the
magnitude of residues, if any, likely to result in milk, meat, poultry
and eggs from such sources.
Beef cattle
Beef cattle were fed with diets spiked with leptophos at levels
of 15, 45, and 150 ppm for 28 days, after which all but one animal at
each feeding level was sacrificed (Bio/toxicological Research
Laboratories Inc., 1971). The remaining animal from each level was
placed on a leptophos-free withdrawal diet for 14 days and then
slaughtered. The results of the analysis of omental fat, muscles and
organs are summarized as follows in Table 4.
TABLE 3. Residues of leptophos and its main metabolites (oxon (II)1, phenol (V) and desbromolepthos (VI) resulting from supervised trials
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
Broccoli head 1971 5 1.35 II,VI 0.25e
1968 5 0.9 V 7.9a 3.8a 1.7a
1969 7 0.45 V 5.0a 2.6a 1.7a
0.9 V 16a 14a 5.2a
Brussels 1970 5-8 0.9 II,V,VI 2.8a 1.6e 0.14c
sprouts
5-8 1.35 II,V,VI 3.6c 3.1b 0.58f
1970 5 0.9 II,V 0.33e
Cabbage 1969 5 0.9 (WP) - 0.28 0.03 <0.01 <0.01
5 0.9 - 0.23 0.01 <0.01
1971 3 0.9 II,V,VI 5.6c 3.9d 3.1d 0.58d 0.05f
1970 6 0.9 II,V,VI 0.40f 0.49e 0.02g
(II 0.07)
1970 5 0.9 II,V,VI 0.18d
0.05f
1970 5 1.35 II,V,VI 0.46d
1971 8 0.9 II 1.2a
1971 4 0.9 II,V,VI 0.08g
TABLE 3. (Cont'd.)
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
1969 3-4 0.9 - 0.96 0.17
3 app 4 app
1969 6 0.9 WP - 0.17
- 0.19
Lettuce 1971 3 1.35(dust) II,V,VI 3.0b 1.5b 0.18d 0.02f
(outdoors)
1971 3 0.9 II,V,VI 35b 20b 16b 0.21d
3 1.80 II,V,VI 50b 30b 22b 0.07g
(II 0.12)
1970 6 0.9 II,V 5.6b 7.0b 3.7c 1.1d 3.4d 0.76e
1971 3 1.80 II,V,VI 28b 4.7b, 3.4c
6.4c 4.1b
Potatoes 1971 4 0.9 II,V,VI 0.02g
(tubers)
0.05g
(V 0.04)
1971 7 1.35 (WP) II,V,VI 0.01g
(II 0.02)
II,V 0.01g
0.05f
(II,V 0.02)
TABLE 3. (Cont'd.)
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
1970 4 0.9 II,V 0.01g
(II 0.06)
1970 4 1.35 II,V <0.01g
(II 0.06)
0.9 II,V <0.01g
(V 0.08)
0.9 (WP) II,V <0.01
(II 0.06)
Tomato 1969 6 0.9 V 1.6b 0.87c 0.83c 0.48c 0.84c
(fruit) 6 0.9 (WP) V 2.0a 0.88b 0.52c 0.31b
1968 5 0.9 V 0.52c 0.56d 0.60d
1968 7 0.9 V 0.25d
0.72c
1970 4 1.35 V 0.35d
0.61c
1971 2 1.35 0.16
0.22
1.35 II,VI 0.76c
1.2c
TABLE 3. (Cont'd.)
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
1971 6 1.02 V,VI 0.88e
1.4b
6 1.02 V,VI 1.6c
1971 6 1.02 - 0.02
0.16
1971 3 1.35 - 0.27
0.35
1971 10 0.9 (WP) II,V,VI 0.70d 0.09g 0.36d 0.06g
(VI 0.12) (II 0.12)
1971 10 1.35 II,V 0.05f 0.21e 0.22e 0.08g (V 0.30)
1970 4 0.9 II,V,VI 1.5d 0.57e 0.32f 0.48e
1970 2 0.9 II,V,VI 2.7d 1.6f
(2 days)
1971 2 1.35 II,V,VI 2.5c
3.4b
(5 days)
Cotton seed 1968 10 0.9 - 0.05-
0.16
(26 days)
whole plant 1970 4 1.35 II,V,VI 0.21f
TABLE 3. (Cont'd.)
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
seed 1970 4 1.35 II,V,VI 0.04f
1971 6 1.35 II,V,VI 0.02g
(34 days)
(II=0.06)
1971 2 1.35 II,V,VI 0.11f
(35 days)
1971 2 0.9 II,VI 0.14f
0.9 II,VI 0.16e
Maize 1969 1 0.9 V 19a 11a 4.3c 0.80d 0.96e 0.80d
(field corn)
whole plant
ear 1968 1 0.9 II <0.01g <0.01g <0.01g
0.04f (II (II
(II 0.03) 0.2,)
0.04) <0.01)
ear 1 1.8 II <0.01g <0.01g <0.01f
(II (II
0.03) 0.03)
stalk 1 0.9 II,V,VI 18b 8.3c 3.5f
19b 8.8c 3.1f
stalk 1 1.8 II,V,VI 23a 13b 11d
8.2b 12b 1.8d
TABLE 3. (Cont'd.)
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
whole plant 1968 1 0.9 II,V 13b 11c 5.4e 3.1e
1 1.8 II,V 21a 18c 11c 0.76g
(V 2.8)
ear 1 0.9 - 0.01 <0.01 <0.01
ear 1 1.8 0.01 <0.01 <0.01
whole plant 1968 1 0.9 II,V 28c 8.0e 5.2f 4.1g
(V 5.0)
ear 1968 1 0.9 II,V <0.01 <0.01 <0.01 <0.01
1 1.8 II,V 52c 22e 18e 12f
Sweet corn 1971 5 0.9 4 II 0.03f
grain + cob 1971 6 1.35 II 0.11e
forage II,V,VI 30c
grain + cob 1971 2 1.35 4 II 0.02e
stalks II,V,VI 26b
30b
grain + cob 1971 7 1.35 II 0.05f
forage II,V,VI 53b
grain + cob 1971 4 1.35 II 0.01f
stalks II,V,VI 20b
TABLE 3. (Cont'd.)
Application (EC Leptophos, mg/kg, at interval (days) after
unless otherwise application.3
stated) Metabolites
Crop Year No. Kg a.i./ha determined2 0-1 3-4 6-8 9-10 14-15 18-22 29-30
Sweet corn for
canning ear 1969 23 0.9 - <0.01,
0.03
stalks II,V 36c,
64b
kernel 1971 22 0.94 II <0.01g
(II 0.05)
cob+husk II,V,VI 9.5b
stalk+leaf 1971 22 0.94 II,V,VI 80b
kernel 1970 4 1.354 II 0.01f
husk+cob II,V,VI 7.6b
11b
stalk II,V,VI 35d
44d
a) Sum of residues of determined metabolites <2% of leptophos residue.
b) Sum of residues of determined metabolites 2-5% of leptophos residue.
c) Sum of residues of determined metabolites 5-10% of leptophos residue.
d) Sum of residues of determined metabolites 10-20% of leptophos residue.
e) Sum of residues of determined metabolites 20-50% of leptophos residue.
f) Sum of residues of determined metabolites 50-100% of leptophos residue.
g) Sum of residues of determined metabolites >100% of leptophos residue.
1 Most of the apparent oxon residue is often a contaminant (see text)
2 II = oxon; V = phenol; VI = desbromo-leptophos
3 Where metabolites exceed leptophos (g) main residue (mg/kg) is also shown in Table
4 Normal application rate, but frequent applications (2-3 day intervals)
TABLE 4. Residues of leptophos and its metabolites in tissues of beef cattle fed fortified diets
Total residue*, mg/kg (Mean of duplicates) Estimated
Leptophos At end of 28-day feeding period After 14-day Reduction half-life
in withdrawal period in fat of total
diet, Omental Omental after 14 residue in
ppm Liver Kidney Muscle fat fat days, % fat, days
15 0.05 0.02 <0.01 0.26 0.13 50 14
45 0.10 0.05 0.02 1.65 0.46 72 7.6
150 0.35 0.35 <0.01 8.48 2.60 69 8.2
* Leptophos + oxon, corrected for artifact, + phenol. Desbromo-leptophos was sought but not detected.
(Detection limit 0.01 mg/kg).
The residues in fat and muscle consisted mainly of the parent
material (92-100%) whereas in the liver and kidney the "phenol"
(metabolite V, Figure 1) predominated at the feeding levels of 15 and
45 ppm.
The highest concentration storage ratio, CSR (level in the tissue
divided by level in the feed), is observed in omental fat. For the
leptophos feeding levels of 15, 45 and 150 ppm, the respective CSRs
are 0.017, 0.037 and 0.057. Dissipation of residues from fat is fairly
rapid (half-life 7-14 days).
Dairy cattle
Johnson et al. (1971) studied the effect of feeding weathered
residues of leptophos including metabolites to dairy cattle. Maize
(field corn) was treated in the field at rates of 0, 0.56, 1.12 and
2.24 kg a.i./ha, harvested, ensiled 1 day later and subsequently fed
to lactating cows for a period of about 8 weeks. All samples were
analysed for leptophos, its oxon and its phenol. The oxon had
disappeared from the silage before feeding began, however, and none
was found in any of the milk samples. All the milk samples contained
leptophos and its phenol in a ratio varying from about 3 to 15. The
results of this study are summarized as follows in Table 5.
TABLE 5. Residues of leptophos and its phenol in silage and in the
milk of cows eating it
Total detectable
Total residue Total residue residue in whole
Leptophos in silage, in silage, Total residue milk, mg/kg
application mg/kg (mean mg/kg (mean, ingested, mean (maximum values
rate, kg/ha wet basis) dry basis) mg/kg body during 8 weeks
weight/day feeding)
0.56 6.77 21.8 0.41 0.037
1.12 16.30 49.5 0.84 0.104
2.24 29.50 91.6 1.71 0.230
One week after the feeding of treated silage was terminated, the
milk of cows fed at the two lower levels was free from residues. Milk
from cows fed at the highest residue level contained an average of
0.012 mg/kg. Bowman (1970) studied the partition of leptophos and its
metabolites between the fat and aqueous phases of milk. He found fat/
water partition coefficients of 3.55 and 1.38 for leptophos and the
phenol respectively. From these figures it can be calculated that, for
milk containing 4% butterfat, the residue levels of leptophos and
phenol in the fat will be respectively 20 and 15 times their levels in
whole milk. In the experiments of Johnson et al., if the residue is
assumed to consist of 90% leptophos + 10% phenol, the total residue
content of the butterfat would be 19 times the whole milk content. The
maximum total residues in the fat would then be 0.7, 2.0 and 4.4 mg/kg
at the three treatment levels, and the corresponding CSRs 0.10, 0.12
and 0.15.
In preliminary residue studies by Bowman and Beroza (1969), pairs
of lactating cows were fed oat silage spiked with 25, 50 and 100 mg/kg
(dry silage basis) of technical leptophos. The average total residue
levels in the wet silage as analysed were 8.6, 17.3 and 30.0 mg/kg
respectively, of which the components averaged 85% leptophos and 15%
phenol. The average total residues in whole milk produced by the three
groups of cows were 0.057, 0.14 and 0.50 mg/kg respectively of which
96% was leptophos and 4% phenol. In comments on this study the authors
stress the possible complication from non-uniform distribution of
leptophos in the experimental feeds. This factor may have contributed
to the disproportionately high residues in milk from the highest
feeding level.
In another study dairy cattle were fed diets spiked at levels of
3, 10 and 38 mg/kg for a period of 28 days. All animals except one at
each feeding level were then slaughtered and the survivor was put on a
12-day withdrawal period.
For the lower two levels of leptophos intake the residues in milk
were below the limit of detection (0.01 mg/kg). The highest feeding
level gave residues in milk on the 27th day of 0.01 and 0.04 mg/kg in
two samples; the phenol residue was too low to be measured. Residues
could not be detected after the 12-day withdrawal period. The residues
in the tissues and organs of cows slaughtered on the last day of
feeding are shown in Table 6; they are corrected for the "oxon"
artifact.
TABLE 6. Residues of leptophos and metabolites in
tissues of cattle fed fortified silage
Leptophos in Total residues, mg/kg
feed, mg/kg Muscle Fat Kidney Liver
9.96 - 0.07 0.01 0.01
- 0.04 0.03 0.03
0.01 0.01 <0.01 <0.01
37.35 <0.01 0.20 0.08 0.12
<0.01 0.21 <0.01 <0.01
trace 0.53 0.05 0.07
Chickens and eggs
In a study carried out at Bio/toxicological Research Laboratories
(1971c), white leghorn chickens received a diet spiked with leptophos
at levels of 0, 0.04, 0.09 and 0.2 mg/kg for a period of 4 weeks
followed by a withdrawal period of 14 days. No residues of leptophos
or its metabolites were detected in eggs one week after withdrawal of
the leptophos at the highest level. The levels of leptophos +
metabolites found in chickens and eggs at the end of the 28 day
feeding period are shown in the following table.
TABLE 7. Residues of leptophos and its metabolites in tissues
and eggs of chickens fed leptophos in the diet
Total residues, mg/kg, at end
Leptophos level of 28-day feeding period
in feed, mg/kg Fat Muscle Eggs
0.04 0.01-0.03* <0.01-0.10* <0.01-0.06*
0.09 <0.01-0.04 <0.01-0.04* <0.01-0.05*
0.2 0.01 <0.01 <0.01-0.02*
* These values probably include some interference by the "oxon"
artifact although partial corrections were made.
FATE OF RESIDUES
In animals
The fate of leptophos in the mouse was found to be qualitatively
similar to its fate in cotton (Holmstead et al., 1973, see next
section). The fate in livestock is partly indicated in the previous
section.
In plants
Holmstead et al. (1973) studied the metabolism of 14C-leptophos,
labelled in the trihalophenoxy and unsubstituted phenyl rings, in
cotton plants under glasshouse conditions. Similar studies were
carried out by Diaz (1973) on tomato plants and by Schwemmer (1973) on
small head lettuce (bibb type).
They found that leptophos did not readily penetrate into the leaf
but was gradually lost from the surface mainly by volatilization. For
example in the experiment on cotton 73-75% of the applied
radioactivity, of which 91-96% was unchanged leptophos, was recovered
1 week after application and 11%, of which about 30% was leptophos,
after 9 weeks. Relatively small amounts of radioactivity were found
inside the leaf. Some of this was extractable with benzene or
methonol, but a significant amount of phenyl-14C was not extractable
and was considered by the authors to be "bound." Its identity was not
elucidated.
It was shown that the primary metabolite detected is the phenol
hydrolysis product (metabolite V, see scheme of metabolism, Figure 1).
Traces of leptophos oxon (II) (corresponding to less than 0.1% of the
applied 14C) were detected occasionally. Of equally low significance
from a residue standpoint is the photo product IV.
The results of the metabolism study on cotton are summarised in
Table 8.
The metabolism studies on tomatoes and lettuce showed similar
results, leptophos itself being the principal residue. The results of
the study on lettuce are summarized in Table 9. Some of the lettuce
metabolites were also found as conjugates, which could be released by
refluxing with 1 N KOH. This treatment yielded 4.9-9.4% of the
recovered radioactivity as metabolite V, 0.3-0.8% as VIII and 0.6-0.8%
as X.
TABLE 8. Metabolism of leptophos by cotton plants
% of recovered radioactivity
Location of 14C label Compound after indicated period (weeks)
1 3 5 9
trihalophenoxy ring Leptophos 91.4 61.4 57.9 42.9
Leptophos-oxon (II) none trace* trace* none
Metabolite V (including
its salt) 8.6 33.1 28.1 29.0
Unknown (bound to pulp) none 5.5 14 28.1
phenyl ring Leptophos 96.4 78.3 68.8
Leptophos-oxon (II) none none none
Metabolite IV 2.3 2.1 7.0
Metabolite VIII 1.3 0.6 2.1
Metabolite X trace* 16.2 10.3
Unknown (bound to pulp) trace* 2.8 11.8
* Less than 0.1% of recovered radioactivity
TABLE 9. Radioactive residues resulting from application of 14C leptophos to lettuce
% of recovered radioactivity
Location of 14C label Compound after indicated period (days)
1 15 24
trihalophenoxy ring Leptophos 98.5 91.7 81.5
Leptophos-oxon (II) 1.1 0.2 0.3
Metabolite V 0.4 3.2 8.8
Metabolite V conjugates - 4.9 9.4
phenyl ring Leptophos 99.8 95.3 90.0
Leptophos-oxon (II) 0.2 0.2 0.3
Metabolite VIII - 1.8 3.1
Metabolite VIII conjugates - 0.8 0.3
Metabolite X - 1.1 5.6
Metabolite X conjugates - 0.8 0.6
Conjugated and bound residues in plants
Schwemmer (1973) compared the efficiency of hydrolysis of
conjugated metabolites by acids, bases and enzymes. He found basic
hydrolysis (3 hours reflux with 1 N KOH) to be the most effective. On
the 14th day after treatment of tomatoes and lettuce, conjugated
residues were respectively 0.7% and 6.5% of the total residue. Much
less effective hydrolysis was obtained with 1 N HCL (3 hours reflux),
beta-glucosidase (4 hours) and beta-glucuronidase (4 hours).
In water
When exposed to sunlight leptophos residues in water decline
fairly rapidly (70-76% loss after 120 hours of exposure) either by
volatilization or breakdown to undetectable moieties. The influence of
pH on the degradation of aqueous solutions of leptophos was studied
(Velsicol, 1971e). There was little degradation below pH 8.3 in the
dark. (At pH 3.1 in the dark at 50°C very little dissipation of
leptophos residues occurred over a period of more than 420 hours.)
Leptophos in water at pH 10.8 and 50°C is rapidly cleaved yielding
O-methyl phosphonothioic acid (compound IV, in Figure 1) and
4-bromo-2,5-dichlorophenol (Compound V).
In soil
Studies on the fate of leptophos residues in soil were carried
out at 4 locations in the USA, where leptophos was applied to the soil
surface at various dosage rates (1-6 kg a.i./ha) (Velsicol, 1971d). In
about 16-30 days 50% of the applied dosage was dissipated. The
remaining residue consisted mainly of the parent compound (80-97%)
together with the oxon, 4-bromo-2,5-dichlorophenol and
desbromo-leptophos. Details are given in Table 10.
TABLE 10. Fate of leptophos residues in soil
Time (days) for Residue, mg/kg in top 5 cm of soil,
decline of applied 28-30 days after application of
leptophos by leptophos (3kg a.i./ha)
Location of study 50% 90% Leptophos Oxon Phenol Desbromo-leptophos
Glendora, Miss. approx 30 < 120 1.61 0.04 0.20 0.03
Arlington, Wis. approx 16 < 90 0.76 0.04 0.08 0.02*
Clayton, N.C. approx <30 < 30* 1.02 0.04 0.62 0.04
Cornelius, Ore. approx 28 90-120 1.05 - 0.52 0.02
* Area hit by hurricane during test; 53 cm rainfall in 24 hours.
The above mentioned study and others in which 14C leptophos was
applied to soil columns (WARF Institute Inc., 1971a), show that
leptophos is adsorbed readily by the upper layers and hardly moves
downwards. Table 11 shows results from the WARF experiments.
TABLE 11. Movement of 14C-leptophos applied to soil columns*
Radioactivity calculated as leptophos, mg/kg
Soil level Sandy loam Silty loam Muck soil Lakeland Fine
top - 7.5 cm 2.0 2.0 3.2 6.0
7.5 - 15 cm 0.2 0.2 0.02 0.03
below 15 cm <0.04 <0.04 <0.04 <0.04
* Height of column 45 cm; 14C labelled leptophos applied at a rate equivalent
to 1.5 kg a.i./ha; simulated rainfall equivalent to 25 cm during the 30-day
test period.
Only trace amounts (<0.1%) of 14C leached through the soil
columns. The residues remaining in the soil were identified as
leptophos. Extraction generally recovered more than 70% of the applied
radioactivity in silty loam, muck soils and lakeland Fine, but only
55-58% in sandy loam.
In a run-off test carried out on a grassy hill (mowed prior to
the application) which sloped 10-15% it was shown that no residues of
leptophos or its main metabolites were found in the water collected 45
and 90 m down the slope; at 9 m down the slope residues of the order
of 0.0001 mg/kg were detected at the 4th and 35th day after
application (WARF Institute Inc., 1971b).
The role of micro-organisms in the degradation of leptophos
residues in soil was studied in sterile and nonsterile soils (WARF
Inst. Inc., 1971a). It was shown that soil bacteria slowly degrade the
residues of leptophos and its metabolites. The rate of residue
dissipation in the laboratory experiments was somewhat slower than the
rate observed in field studies, showing that such factors as
volatilization play a role in the residue loss under field conditions.
Degradation is most rapid after 14 days and is more pronounced at
higher soil moisture levels and higher temperatures.
In storage and processing
Commercial processing of cottonseed reduces leptophos residues.
In pilot studies, hydrogenation and deodorization of cottonseed oil
resulted in a decrease of 92-98% of the initial residue, leading to
residues of 0.04-0.09 ppm in the refined oil.
Removing the wrapper leaves of head lettuce results in a
substantial loss of residues; in normal commercial practice in the USA
and other countries the outer leaves are removed prior to shipment or
marketing.
RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION
No data on residues in food in commerce or at consumption were
available to the Meeting.
METHODS OF RESIDUE ANALYSIS
Bowman and Beroza (1969) developed a GLC method which determines
concurrently leptophos and its main metabolites in milk and maize,
using a flame-photometric detector for the parent compound and the
Oxon and a 63Ni electron-capture detector for the phenol. The
compounds are separated by chromatography of the extract on two
columns; buffer-deactivated silica gel and alumina. Recoveries of the
parent compound and its oxygen analogue added at levels between 0.05
and 5 mg/kg were 91-99% and 72-92% respectively; the recoveries of the
phenol were 55-69% from maize and 93-95% from milk. The limit of
detection for the three compounds is 0.01 mg/kg.
GLC methods for concurrent determination of the parent compound
and the main metabolites including the desbromo-compound in non-fatty
crop samples have been developed by Velsicol. The phenol is
partitioned from the residue extracts with sodium carbonate, dried and
silylated or methylated. The product is then determined by GLC.
Leptophos, its oxon and desbromo-leptophos are determined concurrently
by flame-photometric detection on another GLC column following an
appropriate clean-up procedure. Limits of detection on non-oily crops
are 0.02 mg/kg for the oxon and 0.01 mg/kg for the parent compound,
the desbromo-analogue and the phenol. The method can be adapted for
regulatory purposes. When using the above methods attention has to be
given to possible interference in the determination of the oxon. In a
survey of over 200 untreated check samples about two thirds of the
samples apparently contained the oxon. The frequencies of apparent
oxon residues were highest in food products with a high lipid content.
It became evident that the interfering compound was bis-(2-ethylhexyl
phthalate) a plasticizer component of general plastic laboratory
equipment. Interference by this compound can be largely overcome by
rinsing thoroughly glassware etc. with chromic acid or special
detergents.
NATIONAL TOLERANCES REPORTED TO THE MEETING
The following tolerances were reported.
TABLE 12. National tolerances reported to the meeting
Country
crop mg/kg
Australia
pome fruit (apples and pears) 2
Canada
cabbage 2
lettuce 2
(outer leaves stripped, cabbage and lettuce washed)
Japan
Azuki bean 0.4
cabbage, Chinese cabbage 0.4
potatoes 0.4
rice 0.4
USA*
lettuce 10
tomatoes 2
* Leptophos, including metabolites (oxon, phenol and
desbromo-leptophos), calculated as leptophos.
APPRAISAL
Leptophos is a virtually non-systemic organophosphorus
insecticide with stomach-poison as well as contact action. It is used
on a considerable scale in various countries in Asia, North, Central
and South America, Australia and Europe. The main uses are soil
application against soil-borne insects and foliar application, either
on young plants (seedlings or transplanted plants) or at a later stage
until 3-7 days before harvest. The insecticide is used against a wide
range of insects, especially lepidopterous larvae. Until now no
post-harvest treatment on vegetable commodities has been recommended;
the pesticide is not recommended for use on or near livestock against
ectoparasites etc.
Technical leptophos contains not less than 85% of the pure
compound. The impurities in the technical product are known.
Leptophos is marketed in the form of wettable powder, dust,
emulsifiable liquid and ULV formulations. Concentrations and rates of
application vary, depending on pest, crop and method of application.
Normal application rates are 0.9-1.35 kg a.i./ha. The recommended
pre-harvest intervals in various countries vary considerably for one
and the same crop.
The residue data available were obtained mainly from the United
States. They are from several regions with different environmental and
pest conditions. The data presented for leptophos and its main
metabolites are, with few exceptions, representative of those likely
to result from good agricultural practice.
Extensive information is available on the fate of residues in
plants and their levels in livestock animals. In plants they are more
stable than those arising from many other organophosphorus compounds.
They are eliminated fairly quickly from livestock.
The residues which may occur at harvest in food of plant origin,
following recommended directions for use and Pre-harvest intervals,
usually consist largely of the parent compound and to a smaller extent
of the oxygen-analogue, the phenol (4-bromo-2,5-dichlorophenol) and
desbromo-leptophos [O-(2,5-dichlorophenyl) O-methyl
phenylphospho-nothioate]. On root crops such as potatoes, which show
low levels of total residue, the main compound in the residue is the
phenol.
Only limited information is available on the decrease of residues
of leptophos and its main metabolites during storage and processing,
including household cooking. Hydrogenation and deodorization of crude
vegetable oils resulted in considerable loss of residue.
No information was presented on the carry-over of residues in
tobacco smoke following application on tobacco.
Data on residues and their rates of disappearance were available
from supervised trials on broccoli, Brussels sprouts, cabbage,
lettuce, potatoes, tomatoes, cotton and maize (field corn and sweet
corn). Residue data from other fields of application for which
leptophos is registered and/or recommended were not presented; these
include rice, other small grains, fruit (apples and pears), sugar-cane
and sugar beet.
No information was available on leptophos residues in food moving
in commerce.
Gas-chromatographic procedures are available for specific and
concurrent determination of leptophos and the main metabolites
leptophos oxon, desbromo-leptophos and the phenol. These methods are
suitable or may be adapted for regulatory purposes.
RECOMMENDATIONS
The following guideline levels are recommended as limits which
need not be exceeded when leptophos is used according to good
agricultural practice. They refer to the sum of leptophos, its oxygen
analogue and desbromo-leptophos, expressed as leptophos.
GUIDELINE LEVELS
Pre-harvest intervals on
Limit which recommendations
Commodity mg/kg are based
Broccoli, Brussels sprouts
cabbage 2 28-50
Lettuce 2 28 (outdoor)
Tomatoes 2 7
Crude cotton-seed oil 1 28
Cotton-seed 0.2 28
Cotton-seed meal 0.2 28
Potatoes 0.1 21
Maize: field corn (kernels) 0.05 7
Sweet corn (kernels and cobs,
husks and silk removed) 0.05 3-7
FURTHER WORK OR INFORMATION
REQUIRED (by July 1975)
1. Residue data on other major crops for which recommendations are
made including rice, other small grains, fruit, sugar-cane, sugar
beet.
2. Additional residue data from countries other than the USA.
3. Residues in those parts of agricultural crops which are used
either as such or as agricultural waste for feeding purposes
following normal agricultural practices.
REFERENCES
Bio/Toxicological Research Laboratories, Inc. (1971a) Chicken feeding
study with Phosvel.TM
Bio/Toxicological Research Laboratories, Inc. (1971b) Beef cattle
feeding study. Velsicol Report 107. (Unpublished)
Bio/Toxicological Research Laboratories, Inc. (1971c) Eff fertility,
progeny, viability and residues in eggs and tissues following intake
of Phosvel by chickens. Velsicol Report 106.
Bowman, M.C. (1970) USDA-ARS Report PCT-70-3. Analysis of oat silage,
milk, urine, faeces and blood of cows.
Bowman, M.C. and Beroza, M. (1969) Determination of insecticide,
[O-(4-bromo-2,5-dichlorophenyl)0-methyl phenylphosphonothioate]
(Velsicol VCS-506) its oxygen analogue, and its phenolic hydrolysis
product in corn and milk by gas chromatography. J. agr. Food Chem.,
17(5):1054-1058.
Diaz, L.I., et al. (1973) Radiotracer study of leptophos on tomatoes.
Velsicol. Chem. Corp. Laboratory Report No. 166.
FAO/WHO. (1975) Pesticide Residues in Food. Report of the 1974 Joint
Meeting of the FAO Working Party of Experts on Pesticide Residues and
the WHO Expert Committee on Pesticide Residues. FAO Agricultural
Studies No. ; WHO Technical Report Series No.
Holmstead, R.L., Fukuto T.R. and March, R.D. (1973) The metabolism of
0-(4-bromo-2,5-dichlorophenyl) 0-methyl phenylphosphonothioate
(leptophos) in white mice and on cotton plants. Arch. Environ. Contam.
Toxicol., 1(2):1973.
Johnson, J.C., Jr., Bowman, M.C., Leuck, D.B. and Knox, F.E. (1971)
Persistence of Phosvel in corn silage and effects of feeding dairy
cows the treated silage. J. Dairy Sci., 54(12):1840-1847.
Schwemmer, B.A. (1971a) Heat conversion of VCS-506 to
0-(4-bromo-2,5-dichlorophenyl)-S-methylphenylphosphonate. Velsicol
Chem. Corp. Laboratory Report 83. (Unpublished)
Schwemmer, B.A. (1971b) UV photolysis of leptophos in solution.
Velsicol Chem. Corp. Laboratory Report 86. (Unpublished)
Schwemmer, B.A., et al. (1973) Radiotracer studies of leptophos on
bibb lettuce. Velsicol Chem. Corp. Laboratory Report 167.
TRW/Hazleton Lab. (1971) Continuous feeding and residue study on cows
with technical phosvel (VCS 506). Velsicol Report 108.
Velsicol Chemical Corp. (1967/1971) Residue studies on corn (Field
corn, sweet corn, including sweet corn for canning).
Velsicol Chemical Corp. (1967/1971) Residue studies on potatoes.
Velsicol Chemical Corp. (1968/1971) Residue studies on cole crops
(broccoli, Brussels sprouts, cabbage).
Velsicol Chemical Corp. (1968/1971) Residue studies on cotton and
cotton products.
Velsicol Chemical Corp. (1968/1971) Residue studies on tomatoes.
Velsicol Chemical Corp. (1970/1971) Residue studies on lettuce.
Velsicol Chemical Corp. (1971a) Analysis of technical leptophos for
halogenated dibenzo-p-dioxins. Velsicol Method T 0117.
Velsicol Chemical Corp. (1971b) Analytical method T 0110 B:
Determination of leptophos, its oxon and its phenolic hydrolysis
product in non-fatty crop samples (GLC method).
Velsicol Chemical Corp. (1971c) Analytical method T 0111 B:
Determination of residues of photolytic conversion products of
leptophos.
Velsicol Chemical Corp. (1971d) Analytical method T 0122 B:
Determination of leptophos and its conversion products in soil and
water.
Velsicol Chemical Corp. (1971e) Report 112: Fate of leptophos in
aqueous environments.
Velsicol Chemical Corp. (1973) Analytical method T 0122 A: The
determination of leptophos, its oxon, the desbromo photoproduct and
its phenolic hydrolysis product in crop and animal samples (GLC
method).
Velsicol Chemical Corp. (1974a) Analytical method T 0162:
Determination of 4-bromo-2,5-dichlorophenol residue in crop, animal
and milk samples (methylation method).
Velsicol Chemical Corp. (1974b) Analytical method T 0163: Leptophos,
its oxon, desbromo-leptophos and bromophenol residues in eggs.
WARF Inst. Inc. (1971a) Report: Effects of microorganisms on residues
of leptophos in soil.
WARF Inst. Inc. (1971b) Report: A study of Phosvel; effects on run-off
water.
See Also:
Toxicological Abbreviations
Leptophos (WHO Pesticide Residues Series 5)
Leptophos (Pesticide residues in food: 1978 evaluations)