MONOCROTOPHOS JMPR 1975
Explanation
Monocrotophos was evaluated by the Joint Meeting in 1972
(FAO/WHO, 1973), an acceptable daily intake was established and
recommendations were made for maximum residue limits in a number of
raw agricultural commodities. The Meeting expressed a desire for
further information on the incidence of residues in apples and pears.
Some delegations at the 8th Session of the Codex Committee on
Pesticide Residues were of the opinion that the maximum residue limit
proposed for monocrotophos in apples and pears was too high (Alinorm
76/24, para. 149). After re-examination of the data available to the
1972 Meeting and evaluation of new data, this Monograph Addendum
confirms the necessity for the previously proposed limit for apples
and pears. An increased limit for tomatoes is also recommended.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOCHEMICAL ASPECTS
Biotransformation
It has been shown that monocrotophos and also dicrotophos are not
hydrolysed to the corresponding carboxylic acid by an amidase from
sheep liver which readily hydrolysed dimethoate in this way (Chen and
Dauterman, 1972).
The metabolism and degradation of monocrotophos has been reviewed
recently together with that of several vinyl phosphate insecticides
(Beynon et al., 1973).
TOXICOLOGICAL STUDIES
Special studies on mutagenicity
Mouse
Groups of fertile male CFI mice (12 per group) aged 10-12 weeks
were treated with a single oral dose of 0, 1, 2, 4 mg/kg of
monocrotophos (99% pure). A control group was dosed orally with
dimethyl sulphoxide. Treated and control males were mated with
untreated females for 8 consecutive weeks and 13 days after mating the
females were killed and examined for evidence of dominant lethal
mutations. The number of pregnancies, foetal implantations and early
foetal deaths did not significantly differ from, those in the control
group at any week interval or over the whole 8 weeks (Dean, 1973).
Micro-organism
Technical (77.3% in hexylene glycol), analytical grade (greater
than 99% pure) azodrin and trimethylphosphate (TMPO) have been
examined for mutagenic activity in one strain of S. cerevisiae, 3
strains of S. marcescens and 4 strains of S. typhimurium using a
host-mediated assay (Carworth Farm Strain (CF1) mice) and direct
exposure in vitro; both positive (EMS, NTG) and negative (HOH)
control were used. Mutation rates expressed as revertants to
prototrophy were not detected in the host-mediated assay with
technical azodrin at the highest level tested (8 mg/kg). No mutagenic
effects in the two bacterial systems tested were detected. However,
technical and analytical grade azodrin and TMPO at high concentrations
all caused substantial increases in the conversion frequency at both
adenine and tryphophen loci (Dean et al., 1974).
OBSERVATIONS IN MAN
Groups of healthy male volunteers (3 groups, 6 per group), 18-26
years old and randomly selected from a student population were given
gelatin capsules containing 0, 0.25 mg (3.6 µg/kg bw) and 0.40 mg
(5.9 µg/kg bw) monocrotophos (purity <99% dissolved in 2 mg/ml in 90%
maize oil and 10% acetone mixture) each day for a period of 30 days.
Plasma and erythrocyte ChE activities were measured prior, during and
for 12 days after exposure. The plasma ChE activity of the 0.25
mg-group reached a stable level of 87% of its initial value after two
weeks while that of the 0.40 mg-group showed a decline to 78% of its
initial activity after 28 days and to 77% on the 29th day. Neither
group showed a decline in the average activity of erythrocyte ChE.
Liver functions (GOT, GPT and alkaline phosphatase) showed no
significant changes (Verberk, 1972).
Comments
Monocrotophos was previously evaluated in 1972 and an ADI of
0-0.0003 mg/kg body weight was estimated. Additional data was reviewed
with respect to mutagenesis, biotransformation and its effect on man.
In vivo and in vitro studies with mice and micro-organisms reflect
the lack of mutagenic potential. An extensive study with human
volunteers demonstrated no significant cholinesterase depression over
a 30 day test period. A slight depression of plasma cholinesterase was
rapidly reversed on cessation of exposure. Based on the slight plasma
cholinesterase depression in human studios, rapid recovery of enzyme
activity, lack of erythrocyte cholinesterase depression and additional
evidence of safety based on negative mutagenic potential, the Meeting
reconsidered and increased the ADI for man.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 0.5 ppm in the diet equivalent to 0.025 mg/kg bw
Dog: 0.5 ppm in the diet equivalent to 0.0125 mg/kg bw
Man: 0.006 mg/kg bw
Estimate of acceptable daily intake for man
0-0.0006 mg/kg bw
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERN
Although the quantity of monocrotophos used annually has
increased considerably, there does not appear to be any significant
increase in the field of usage beyond that evaluated by the Joint
Meeting in 1972.
The usefulness of monocrotophos as a spray for deciduous crops,
particularly apples, has resulted in it becoming one of the most
widely used insecticides for apples and pears in Australia and Italy.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Apples
The extensive data examined by the Joint Meeting in 1972 revealed
that following the application of 0.04% monocrotophos spray 4 weeks
before harvest, residues on apples ranged from, <0.01 to 1.5 mg/kg.
It was noted at the time that the upper figures, however, were derived
from experiments in which the spray was applied by hand, which usually
requires somewhat higher volume. It was considered that in practical
conditions of use, 1.0 mg/kg would be the highest level likely to
occur.
The extensive data have been re-examined and a selection of the
results are included in Table 1.
From the data summarized in Table 1, it is quickly apparent why
the Meeting recommended that a maximum residue limit of at least 1
mg/kg would be required to cover residues resulting from the approved
use of monocrotophos on apples. It should be emphasized that all these
data were collected from supervised trials in which the insecticide
was applied by hand spraying.
Since these data were generated, the recommendations for use have
not greatly changed. The spray concentration remains 0.025-0.04%
active ingredient and the interval between last treatment and harvest,
4 weeks. However, it has become apparent that in Australia most of the
monocrotophos used is applied by air-blast sprayers and not hand
equipment as in most previous trials. Machine-spraying leads to the
use of lower volumes per tree and hence smaller amounts of total
product applied.
New residue data, summarized in Table 2, have been developed from
commercial orchards where monocrotophos is applied by air-blast
machine as in Australia. Table 2 also includes some additional data
from Italy on residues resulting from machine spraying which were not
available when the original information was reviewed in 1972.
The new data indicate that residues from machine spraying will be
lower than where hand equipment is used, and the Australian data are
considered to give better guidance on residue levels likely to arise
in commercial practice in Australia than the higher levels reported in
the 1972 monographs. As may be seen, the new data indicate lower
residue levels than the old data and would seem to be compatible with
a maximum residue limit of 0.5 mg/kg for apples. However, in the case
of Italy, the higher levels reported in the 1972 monographs which are
summarized in Table 1, are still regarded as representative of much of
current commercial practice and these suggest that for apples a
maximum residue limit of 1 mg/kg is still needed.
It is interesting to note that in the 1975 Australian trials
(Table 2), the level of residues found in the peeled fruit and in the
whole fruit were similar. This is not unexpected in view of the
systemic properties of this insecticide.
Pears
In assessing the data in 1972, the Meeting came to the conclusion
that the level of monocrotophos residues in pears treated in
accordance with good agricultural practice was such that a maximum
residue limit of 1 mg/kg was appropriate. This deduction has been
questioned by some delegates of the Codex Committee on Pesticide
Residues and the Meeting therefore re-examined the extensive data
available to the Meeting in 1972.
A summary of the information examined in 1972 is set out in Table
3. It is clear that the residues resulting from, the application of
monocrotophos sprays at or below approved rates are at least equal to
and often exceed 0.5 mg/kg when fruit Y harvested 4 weeks after the
last application. As far as can be judged from, these data, the
half-life of the residue in mature fruit is not much less than 4
weeks. This is to be expected in view of the systemic properties of
monocrotophos.
TABLE 1. Monocrotophos residues in apples resulting from hand spraying
Residues mg/kg after pre-harvest interval (weeks)
Spray No. of
Country Variety Concn, % Applications 2 3 4 5 6 7 8 9 10 12
Australia Jonathan 0.04 7 1.9 1.0 0.7
Prince Alfred 0.04 2 0.19
" 3 0.94
" 4 1.2
" 5 2.1
Democrat 0.04 1 1.9 0.7 0.96 0.68 0.94 0.99 0.67 0.46
Granny Smith 0.04 1 0.92 0.86 0.70 0.46 0.44 0.55
Unknown 0.04 Unknown 1.3 0.25
Golden Delic. 0.04 " 0.84
Jonathan 0.04 " 0.19
Granny Smith 0.04 " 0.09 <0.01
Jonathan 0.04 "
" 0.04 " 0.34
" 0.02 4 0.18
" 6 0.51
" 9 1.8
" 0.038 2 0.26
" 3 0.48
" 4 0.48
" 5 2.1
Rome Beauty 0.038 5 1.5
Italy Star King 0.025 2 0.95
Democrat 2 1.0
Abbondanza 2 0.8
Star King 2 1.0
Abbondanza 0.05 5 0.5
Unknown 0.03 4 0.25 0.2 0.19 0.18
TABLE 2. Monocrotophos residues in apples resulting from mechanical spraying
Interval Monocrotophos residues
between Pre-harvest mg/kg
Spray No. of treatments interval Whole fruit Peeled fruit
Country Year Variety concn. % applications (weeks) (weeks) (1) (2)
Australia 1975 Granny Smith 0.038 3-4 3-4 3 0.14 0.13
" 1975 " " " " 5 0.12 0.08
" 1975 " " " " 3 0.43 0.36
" 1975 " " " " 3 1/2 0.66 0.54
" 1973 " " 4 4, 4 & 9 4 0.13 0.12
Italy 1970 Imperatone 0.025 2 3 4 0.11 -
" 1970 Golden
Delicious " " " " 0.53 0.40
" 1970 Stark
Delicious " " " " 0.37 -
(1) Average weight of whole apple 150g.
(2) The peel accounted for 17% of the weight of the apples
In order to ascertain the effect of the application method on
residue levels, the results of trials carried out in Italy using hand
application methods (Table 3) were compared with data obtained from
other Italian trials where the insecticide was applied with mechanical
equipment (Table 4). The amount of residue remaining after mechanical
application cannot be judged to be lower than that found in fruit
sprayed by hand.
In order to confirm these observations, further trials were
carried out in Australia in 1975 using standard spray concentration
and a minimum number of applications applied at intervals consistent
with normal practice in the area. At least half of the data indicate
residues at or above 0.5 mg/kg in fruit harvested 3 to 7 weeks after
the last treatment. (Table 4).
Once again the residue studies indicate that the residue is
distributed relatively evenly through the whole fruit, the peeled
fruit containing substantially similar amounts of residue to the
un-peeled.
On the basis of the data from these supervised trials, the
previously recommended maximum residue limit for monocrotophos on
pears must be confirmed.
Tomatoes
Because of the dependence of tomato growers on organochlorine
insecticides for the control of Heliothis and other lepidopterous
pests, there is an urgent demand for an alternative insecticide which
is environmentally acceptable. Because of its efficacy against
Heliothis and other lepidoptera, there has been considerable interest
in the use of monocrotophos for the control of these pests on
tomatoes.
The 1972 Meeting evaluated extensive data, then available, and
recommended a maximum residue limit of 0.5 mg/kg for monocrotophos on
tomatoes. Examination of the data published in the 1972 monograph
(FAO/WHO 1973) indicates that it is only possible to keep within this
limit if the tomato crop is not sprayed within 4 weeks of harvest.
Since tomatoes flower and fruit over a long period and since
fruit at every stage from bud to fully ripe fruit can be found on the
vine at one time, it is not possible to utilise monocrotophos in a
manner which would protect the crop against insect damage without
possibly producing residues in excess of the 0.5 mg/kg maximum residue
limit. The Meeting, therefore, re-examined the data submitted in 1972
and considered this in conjunction with results of supervised residue
studies which have since became available. A summary of a
representative selection of these data is set out in Table 5.
TABLE 3. Monocrotophos residues in pears resulting from hand spraying
Residues (mg/kg) after pre-harvest interval (weeks)
Spray No. of
Country Variety concn. % applications 1 2 3 4 5 6 7 8 9 10 12
Australia 0.04 7 0.2 0.2 0.2 0.1
Australia 0.04 4 0.54
" 0.03 4 0.76
" 0.04 3 0.61
Italy 0.01 2 0.60
" 0.01 2 0.08
" 0.028 1 0.24
" 0.056* 1 0.35
" 0.028 1 0.25
" 0.056* 1 0.29
" 0.025 2 0.15
" 0.025 4 0.99 0.72 0.54 0.47 0.54
* Above recommended dosage.
TABLE 4. Monocrotophos residues in pears resulting from mechanical spraying
Interval Monocrotophos residues
between Pre-harvest mg/kg
Spray No. of treatments interval Whole fruit Peeled fruit
Country/Year Variety concn. % Applications (weeks) (weeks) (1) (1)
Australia 1975 Packhams 0.038 3-4 3-4 7 0.50 0.48 (2)
" 2 0.76 0.50 (2)
" 3 1/2 0.51 0.46 (2)
" 4 1/2 0.26 0.23 (2)
" 6 0.20 0.14 (2)
Italy 1970 Passacrassana 0.025 3 2 4 0.28 0.17 (3)
4 0.21 -
4 0.18 -
4 0.18
(1) Average weight of a whole pear 130g.
(2) The peel accounted for 15% of the weight of the pears.
(3) The peel accounted for 22% of the weight of the pears.
The most noticeable feature of the data is the slight decline in
the level of residues between the 1st and 28th day after application.
This is perhaps not unexpected in view of the systemic properties of
the insecticide and the growth pattern of the crop.
On the other hand, the data indicate that the number of
applications has very little bearing on the level of residues
resulting from the treatment. The level of residues resulting from 19
successive applications to not significantly higher than that
resulting from 3 applications of the same concentration of spray.
Tomatoes grown under a standard regime of monocrotophos sprays were
submitted for residue analysis both before and after washing with
water. Generally, though a measurable amount of residue is removed by
washing, it is only a small proportion of the total. In view of the
fact that monocrotophos is moderately soluble in water, this result
would be surprising were it not for the knowledge that the bulk of the
residue is located well within the fruit. Such residues are
accumulated by the systemic uptake of spray deposited not only on
fruit but on leaves and stem also.
Evidence of residues in food in commerce or at consumption
As discussed earlier in this monograph addendum, and as indicated
in Tables 2 and 4, there is every indication that residues resulting
from approved application of monocrotophos to apples and pears are
distributed throughout the fruit and would not be removed by washing
or peeling in preparation for consumption.
Likewise, in the case of tomatoes the residue is not
significantly decreased by washing in preparation for eating and it
must therefore be concluded that the bulk of the monocrotophos
residues present in raw agricultural commodities will remain, at the
time of consumption, in foods which are not cooked.
In Australia in 1973 a survey was carried out in one district
where monocrotophos is used by most of the apple and pear growers.
Fruit delivered to the packing-house by growers was sampled at random
for analysis for monocrotophos residues. In none of the samples were
residues of monocrotophos found to be above 0.5 mg/kg. The data
indicate that most of the fruit contained no more than 0.15 mg/kg.
APPRAISAL
The 1972 Joint Meeting proposed a temporary maximum residue limit
for monocrotophos in apples and pears of 1 mg/kg, with a comment that
further data would be desirable.
TABLE 5. Monocrotophos residues in tomatoes
Monocrotophos residues (mg/kg) after pre-harvest intervai (days)
Dosage rate No. of
Country kg/ha applications 1 3 5 7 10 14 21 28 35 42
South Africa 0.2 3 0.14
" 2 0.13
" 1 0.02
0.4 3 0.64
" 2 0.51
" 1 0.02
0.47 3 <0.01
" 6 0.06
0.94 3 0.08
" 6 0.34
0.2 2 <0.01
3 0.01
U.S.A. 1.0 3 1.5 1.1 0.07 1.1 0.44 0.33
1.0 19 1.86 1.15 1.28 0.90
2.0 19 2.80 3.03 1.91 1.02
1.0 7 0.51 0.30 0.22 0.31
0.8 7 0.59 0.57 0.46 0.54
Australia 0.06% ai 5 1.2
" 6 1.4
0.05% ai 3 0.42
" 4 0.36
" 5 1.1
" 6 1.1
" 7 1.6
1.2 7 0.12
" 8 0.25
" 9 0.37
3.3 4 1.1 0.82 0.79 0.31
TABLE 5. (Continued)
Monocrotophos residues (mg/kg) after pre-harvest intervai (days)
Dosage rate No. of
Country kg/ha applications 1 3 5 7 10 14 21 28 35 42
Puerto Rico 1.25 5 0.35
Switzerland 0.02% ai 1 0.45 0.16 0.16 0.17 0.12
" 1 0.38 0.10 0.07 0.05 0.04
Guatemala 1.0 10 0.67
0.6 5 0.03
TABLE 6. Monocrotophos residues in tomatoes before and after washing
Dosage rate No. of Pre-harvest Monocrotophos residues (mg/kg)
Country kg/ha Applications interval (days) Before washing After washing
Puerto Rico 1.25 5 27 0.29 0.25
" " 5 27 0.40 0.28
U.S.A. 1.0 5 23 0.14 0.09
" " 5 23 0.24 0.15
" " 5 25 0.30 0.17
" " 5 25 0.21 0.17
" " 5 30 0.08 0.12
" " 5 30 0.12 0.16
The original data on which the proposed maximum residue limit was
based were developed from supervised trials in Australia and Italy,
the two countries employing monocrotophos on pome fruit. Although in
the meantime the use recommendation has not greatly changed, it has
become apparent that in Australia the majority of the monocrotophos is
applied by air-blast sprayers and not hand equipment as used in the
supervised trials. The use of machine spraying leads to the
application of smaller volumes and hence smaller amounts of total
product applied. New residue data have been developed to cover this
use in Australia.
These new data have been examined alongside the raw data
available in 1972 and some additional data from Italy which were not
available to the 1972 Meeting.
The new data indicate that residues resulting from machine
spraying will be somewhat lower than those resulting from the use of
hand-held equipment but the difference is only slight. Although the
new data are considered to give better guidance on residue levels
likely to arise in commercial practice in Australia, the somewhat
higher levels found following hand spraying and reported in the 1972
monograph are still regarded as representative of much current
commercial practice in Italy.
The data clearly indicate that, owing to the systemic nature of
the insecticide, there is relatively little loss of residue from fruit
in the 4 weeks which elapses between application and harvest. Because
of the substantial variation in the level of residues resulting from
comparable application procedures, the Meeting judged that it would be
unwise to recommend maximum residue limits lower than the 1 mg/kg
recommended in 1972. Among numerous results from many supervised
trials, there were certainly enough data to indicate that in
commercial practice there could well be a significant number of lots
with residues well above 0.5 mg/kg.
Because of increasing interest in the use of monocrotophos for
the control of insect pests of tomatoes, the Meeting re-examined the
data submitted in 1972 and considered new data which had since become
available. It is obvious that monocrotophos could not be used
effectively in controlling pests of tomatoes without a substantial
proportion of samples having residues above 0.5 mg/kg. The Meeting
therefore recommended that the maximum residue limit on tomatoes be
increased from 0.5 mg/kg to 1 mg/kg.
RECOMMENDATIONS
The previously recommended maximum residue limits for apples and
pears are confirmed, and the limit for tomatoes is amended.
MAXIMUM RESIDUE LIMITS
Commodity Limit mg/kg
Apples, pears, tomatoes 1
FURTHER WORK OR INFORMATION
Desirable
As FAO/WHO 1973a, p. 45, excluding item 2.
REFERENCES
Beynon, K. I., Hutson, D. H. and Wright, A. N. (1973) The metabolism
and degradation of vinyl phosphate insecticides. Res. Rev., 47: 55-142
Chen, P. R. S. and Dauterman, W. C. (1972) Studies of the toxicity of
dimethoate analogues and their hydrolysis by sheep liver amidase.
Pest. Biochem. Physiol., 1:340-
Dean, B. J. (1973) Toxicity studies on Azodrin: dominant lethal assay
in male mice after a single oral dose of Azodrin. Unpublished report
from the Shell Tunstall Research Laboratory, Sittingbourne. Submitted
to WHO by Shell Co.
Dean, B. J., Doak., Somerville, H. A and Whitebread, C. (1974)
Toxicity studies with Azodrin: effect of AzodrinR on micro-organisms
in the host mediated assay and in vitro. Unpublished report from the
Shell Tunstall Research Laboratory, Sittingbourne. Submitted to WHO by
Shell Co.
Verberk, M. M. (1972) Cholinesterase inhibition in man caused by 30
days administration of monocrotophos. Unpublished report from the
Coronal Laboratory, University of Amsterdam. Submitted to WHO by Shell
Co.
See Also:
Toxicological Abbreviations
Monocrotophos (HSG 80, 1993)
Monocrotophos (ICSC)
Monocrotophos (WHO Pesticide Residues Series 2)
Monocrotophos (Pesticide residues in food: 1991 evaluations Part II Toxicology)
Monocrotophos (Pesticide residues in food: 1993 evaluations Part II Toxicology)
Monocrotophos (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)