FENITROTHION JMPR 1974
Explanation
In 1969 the Joint Meeting evaluated fenitrothion in the light of
the information then available. Recommendations were made for a
temporary ADI, temporary tolerances on a number of raw agricultural
commodities and practical residue limits for meat and milk (arising
from the use of fenitrothion for locust control).
The Meeting listed seven items of further work or information
required before the temporary recommendations could be confirmed as no
longer temporary and before recommendations for additional tolerances
could be made (FAO/WHO, 1970).
Since that time a considerable amount of additional research has
been carried out to provide information and answers to the
requirements laid down in 1969 and in addition the Meeting had
available many additional published and unpublished reports relating
to fenitrothion, its properties, residues, toxicology and analysis.
This Information has been considered and the following monograph
addendum has been prepared.
IDENTITY
Relevant Chemical Properties
Because of the many and varied uses to which fenitrothion
preparations are applied it is important to recognize that the
performance, toxicity, residues and environmental effects depend
largely on the quality of the technical product which in turn will
depend on the method of manufacture and the conditions of storage. In
response to the requirement of the 1969 Joint Meeting one of the
largest and most experienced manufacturers of fenitrothion has
provided information on the impurities in the technical grade
material. These are given in Table 1 (Sumitomo, 1974). Results of
analysis of 9 samples of technical fenitrothion are given in Table 2
(Greenhalgh, 1974a). The importance of the S-methyl isomer, its
properties, methods of determination and occurrence in technical
fenitrothion were discussed by Greenhalgh et al. (1974). According to
these workers the content of the S-methyl isomer varies slightly
depending upon the method of determination and in the seven samples
examined ranged from 0.55% to 4.41%. These samples are included in
Table 2. It must be recognised that the age and storage histories of
these samples are not known and therefore no conclusion as to the
relative purity of the original materials may be drawn. The results in
no way reflect the purity of the technical grade fenitrothion
presently available from these manufacturers nor do they necessarily
represent the impurities in commercial formulations, which are often
stabilised.
Recently, a GLC method has been developed for the determination
of the S-methyl isomer in fenitrothion. It is sensitive to 0.1%
(Kovacicova et al., 1973; Greenhalgh et al., 1974).
A high speed liquid chromatographic method permits the
simultaneous monitoring of each of the impurities without clean-up to
a limit of determination below 0.1% (Marshall et al., 1974).
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOCHEMICAL ASPECTS
Biotransformation
Metabolic studies on fenitrothion are described in the 1969
evaluation (FAO/WHO, 1970). Fenitrothion is metabolised by Bacillus
subtilis to amino-fenitrothion, desmethyl-aminofenitrothion,
desmethyl-fenitrothion and dimethyl phosphorothioic acid. Even resting
cells of the bacteria easily reduced the compound. Fenitrooxon and its
metabolites were not detected. Amino-fenitrothion is presumed not to
have biological activity (Anon., sine data, a).
TABLE 1. Impurities in technical grade fenitrothion.
Component Percentage
active ingredient (by colorimetric method) 95-98
(95% up)
O-methyl O,O-di(4-nitro-M-tolyl) phosphorothioate 2-3
O-methyl S-methyl O-(4-nitro-M-tolyl)
phosphorothioate 0.5-1
O,O-dimethyl phosphorochloridothioate <0.5
3-methyl-4-nitrophenol <0.2
toluene <0.1
water <0.1
Effects on enzymes and other biochemical parameters
Intraperitoneal injections of 25 mg/kg of fenitrothion in mice
inhibited aminopyrine demethylase and aniline hydroxylase activities
in the liver by about 50%. Similar effects on drug metabolising enzyme
activity were observed in female but not male rats. Administration of
fenitrothion to mice prolonged the hexobarbital sleeping time and also
suppressed the oxidative metabolism of parathion by their livers in
vitro. Oxidative drug metabolism by liver was also inhibited by
addition of fenitrothion (IC50 of 10-5M) to the test system in
vitro (Uchiyama et al., 1974).
TABLE 2. Analysis of technical grade fenitrothion 1, 2 (Greenhalgh, 1974).
S-Methyl 4-Nitro- S-Methyl-bis-
Sample fenitrothion 3-methylphenol Fenitrooxon Bis-fenitrothion fenitrothion
Accothion 1.63 0.22 <0.1* 0.38 <0.05*
Accothion ULV 0.90 0.25 0.44 0.22 <0.05*
BASF (Canada Ltd) 4.41 0.10 <0.1* 0.64 0.14
Metathion 2.14 0.16 0.23 <0.01* <0.05*
Metathion CHJZD 3.36 0.36 <0.1* 1.02 <0.05*
Novathion 2.37 0.20 <0.1* 0.54 0.40
Sumithion Technical 0.55 0.16 <0.1* 0.48 <0.05*
Sumithion E-50 1.26 1.45 <0.1* <0.01* <0.05*
Sumithion <0.05* <0.004* <0.1* 1.35 <0.05*
1 The history of those samples, date of manufacture and storage conditions are unfortunately
unknown. As such, these results cannot be taken as an evaluation of each manufacturer's
product (Marshall and Greenhalgh, 1974).
2 Determined by high speed liquid chromatography.
* Not detected.
Female rats were given single oral doses of 200 mg/kg bw of
fenitrothion and/or malathion. The level of fenitrothion in the liver
was decreased in those animals that received both compounds, in
comparison to those receiving only fenitrothion. However, after an
initial decrease there was an increased content of fenitrothion in
blood and muscle of the rats that received malathion as well.
Fenitrooxon, the toxic metabolite of fenitrothion, increased markedly
with time in blood and muscle of rats given fenitrothion and malathion
in combination, in contrast to rats given only fenitrothion, where
there was a rapid peak and decline in fenitrooxon concentrations.
Liver fenitrooxon concentrations were not appreciably altered by the
combined dosage regimen. These studies suggest the possibility for
potentiation of fenitrothion by malathion, but actual tests for
potentiation were not conducted (Hladká et al., 1974).
TOXICOLOGICAL STUDIES
Special studies on mutagenicity
Three tests for mutagenicity were performed using microbial
systems. Using tryptophan auxotrophic mutant and UV repair deficient
strains of E. coli K 12, cultures were exposed to fenitrothion
concentrations of 0, 13.2, and 132 µg/ml in a dimethylsulfoxide
saturated solution. The same concentrations except the 132 µg/ml were
used with coli-phage lamba 1847 sus E- h+. No mutagenic and radio
mimetic action was detected (Suzuki et al., 1974).
Mutagenic activity of fenitrothion was studied in rats given 0,
10, 40 and 80 ppm of fenitrothion in the diet during a 4-generation
reproduction study. The study combined the dominant lethal test in a
single mating (in the course of one week) with P - to F3 generation
males and females following 200 days of exposure, and at individual
stages of spermatogenesis with 15 males of F2 and F4 generation in
each group after an exposure of 100 days and mated each week with 30
unexposed females for 10 weeks. Chromosome aberrations were analysed
in the bone marrow of F2 generation males following 200 days of
exposure, and of F3 generation males following 500 days of exposure
to a dose of 80 ppm. The results were negative in all tests both in
relation to dose and generation (Benes et al., 1974a).
Special studies on neurotoxicity
Hen
Groups of adult hens, eight, six and three respectively, were
orally given single doses of 250, 500 or 1000 mg fenitrothion/kg bw.
300 mg/kg of TOCP was used as a positive control. Toxic symptoms,
which lasted 4-10 days occurred in all groups. One half of the hens of
the middle dosage group and all from the highest fenitrothion group
died within 24-48 hours post-treatment. No delayed paralysis of the
legs occurred at any dose group or at any time during the 5-week
observation period, while all TOCP dosed animals developed paralysis
within 3 weeks. The sciatic nerves of all the surviving hens given
fenitrothion were normal.
A group of 16 hens was given 500 mg fenitrothion/kg and
immediately after atropine and 2-PAM was given to protect against
acute anti-cholinesterase effects. None of the surviving hens (12 out
of 16) showed delayed paralysis during the 21 day observation period.
Groups of 8 hens were given 33.4 or 16.7 mg fenitrothion/kg/day,
6 days per week for 4 weeks and then observed for another 3 weeks.
Slight toxic symptoms were seen in both groups during the
administration and one hen of the highest group died on the 5th day.
Body weights were decreased in both groups, but the decrease for the
lower group was transient. No paralysis nor histopathological changes
in the sciatic nerve or spinal cord were recorded (Kadota et al.,
1974a).
Special studies on potentiation
Rat
The effects of combinations of fenitrothion with 4 other
organophosphates were studied in male rats and it was found that only
the combination with malathion was more than additive and that
fenitrothion could be considered the "potentiator." The potentiation
(one half expected LD50) was most pronounced at the combination of
1:1 (Benes and Cerna, 1970).
Special studies on reproduction
Rat
A three-generation reproduction study in rats was started using
15 males and 30 females per test-group (20 males + 40 females control)
at dietary levels of 10, 30 and 150 ppm. After the first filial
generation (F1a) the study continued using 10 males and 20 females
per dietary level of 0, 10, 30 and 100 ppm. Fertility, gestation,
lactation and live birth indices were compared. In the P1 and
P2-generation animals, 150 and 100 ppm of fenitrothion in the diet
caused weight reduction in the parental animals as well as in the body
weights of both sexes at weaning and suppressed lactation indices
(number of pups weaned divided by the number of pups nursed) through
all generations. The groups fed the highest dose level also showed a
higher incidence of cannibalism and/or smallness at weaning whereas
all litters seemed normal at birth. No dose-related malformations or
histopathological changes were seen (Rutter and Voelker, 1974b).
Groups of 10 male and 20 female rats were fed a diet containing
0, 10, 40 and 80 ppm technical fenitrothion (with maximum 0.5%
p-nitro-m-cresol) in a 4-generation, 2-litter per generation
reproduction study. The following parameters were studied: body weight
and food consumption of the parental animals and indices of fertility,
gestation, live birth, 24-hour survival, 5-day survival and lactation;
gross pathology of all pups, organ weights and histopathological
examination of F4b weanlings; cholinesterase activity in whole blood
in males of F2a (aged 15 weeks) and in all weanlings of F4b (aged 4
weeks). Fertility, gestation and live birth indices were normal in all
groups, whereas the 24-hour and 5-day survival indices were reduced in
one or both litters of the 80 ppm group in almost all generations. The
lactation index was reduced in all generations of the 40 and 80 ppm
groups. The mean litter size was smaller in all but five test litters,
but the occurrence was without a clear dose-dependence. The lowest
number of pups was, however, found in six of eight litters in the 80
ppm group. The mean weight of the pups at birth and at 21 days of age
was normal whereas the growth of the parental animals was slightly
decreased in the 80 ppm group. Cholinesterase activity was decreased
in relation to dose and length of exposure; in the 10 ppm groups the
decrease was only slight. Organ weights, gross and microscopic
pathological examinations revealed no abnormalities (Benes et al.,
1974b).
Rabbit
Groups of female albino rabbits were inseminated (gestation day
0) and on gestation day 6 through 18 inclusive were dosed with 0, 0.3
or 1 mg fenitrothion/kg/day in gelatine capsules. A positive control
group given 37.5 mg thalidomide/kg/day was included. The compound had
no effect on the does nor on the number of implantation sites, early
or late resorption sites, number of dead or live young or aborted
foetuses. In the thalidomide group approximately 10 per cent of the
foetuses showed external malformations, while none were seen in the
other groups. No effects related to the administration of fenitrothion
were seen on examination for internal or skeletal deformities (Ladd,
1971).
S-methyl isomer of fenitrothion
The S-methyl isomer of fenitrothion (SMF) occurs as an impurity
(in the order of 0.5 to 1.5%) of technical fenitrothion. SMF can also
be formed by thermal isomerization of fenitrothion or by UV
irradiation-catalyzed isomerization during prolonged storage under
inappropriate conditions. The acute oral toxicity in rats and mice of
SMF was approximately twice that of fenitrothion, and the signs of
poisoning were typical of the muscarinic and nicotinic action of
acetylcholine seen with anticholinesterase compounds. The in vitro
anticholinesterase action of SMF was compared with that of
fenitrothion and its oxygen analogue using human and horse serum and
fly head cholinesterases. The pI50 values for SMF were: horse serum
7, human serum 8, and fly head 9; while for fenitrothion the values
were: human and horse sera 5, fly heads 6. The oxygen analogue of
fenitrothion was about equal to SMF as a direct cholinesterase
inhibitor. These results indicate that contamination of fenitrothion
by SMF can account for much of the anticholinesterase action of
technical fenitrothion, and that this should be considered if in
vitro tests are used for anticholinesterase assay purposes. SMF was
more rapidly degraded than fenitrothion in rats, as shown by measuring
the rates of excretion of p-nitro-m-cresol. Furthermore, a greater
proportion of the total dosage of SMF could be accounted for by this
urinary metabolite. Four groups of 10 male rats each were orally dosed
with 0, 1, 6 and 12 mg/kg and were mated with untreated female rats
(20 per group). There were eight sequential matings with a new group
of females each week. There was slightly greater number of resorptions
in the treated groups; and although there was not a marked difference
between the three test groups, the investigators concluded that SMF
had a low order of mutagenic action (Rosival et al., 1974; Kovacicová
et al., 1973).
Acute toxicity
TABLE 3. Acute toxicity of fenitrothion
Animal Route LD50 mg/kg bw References
Mouse (M) oral 1030 Miyamoto and Kadota,
1972
Mouse (F) oral 1040 ibid.
Rat (M) oral 330 ibid.
Rat (F) oral 800 ibid.
Ringneck
pheasant oral 34.5 Fletcher, 1971e
Mallard duck oral 2550 Fletcher, 1971f
Dog oral min. lethal
dose 681 mg/kg Mastalshi, 1971c
Rat (M) oral 940 Benes and Cerna,
1970
Rat (F) oral 600 ibid.
TABLE 4a. Acute toxicity of fenitrothion metabolites - Fenitrooxon.
Animal Route LD50 mg/kg bw References
Dog oral min. lethal Mastalski, 1971a
dose = 68.1
Ringneck
pheasant oral 10.6 Fletcher, 1971a
Mallard duck oral 12.5 Fletcher, 1971b
TABLE 4b. Acute toxicity of fenitrothion metabolites
- 3-methyl-4-nitrophenol (p-nitro-m-cresol)
Animal Route LD50 mg/kg bw References
Dog oral min. emetic Mastalski, 1971b
dose = 680 mg/kg
Rat (F) oral 1200 Anonymous, 1971
Rat (M) oral 2300 Anonymous, 1971
Ringneck
pheasant oral 4640 Fletcher, 1971c
Mallard duck oral 1470 Fletcher, 1971d
Short-term studies (metabolite)
Groups of rats (15 males and 15 females) were given 0, 150, 500
and 1500 ppm of 3-methyl-4-nitrophenol (p-nitro-m-cresol) in the diet
for 6 months. No dose-dependent changes were found in blood or
urinalysis, biochemical studies, organ weights or after
histopathological examination, except a transient excretion of sugar
in the urine of rats fed 1500 ppm (Anon., sine data, b).
Short-term studies (fenitrothion)
Rat
Groups of 8 male and 8 female rats were fed diets containing 0,
10, 50 and 250 ppm of fenitrothion for 34 weeks. In another test,
groups of 16 rats of each sex were fed fenitrothion at 0, 5, 25 and
125 ppm, for the same period. The feeding of 250 ppm resulted in a
decrease in body weight gain of the females. In the 125 ppm group a
lower relative weight of the spleen of both sexes was found. However,
only the females of the 250 ppm group showed histological changes of
the liver and spleen. The cholinesterase activities were measured at
intervals in both plasma and erythrocytes and a dose-dependent
decrease was found in all test groups, except in plasma from the males
at 5 ppm. In the females the depression was slight. The activity in
the brain was decreased only in the 250 ppm groups.(Benes and Cerna,
1970).
Groups of rats (15 males and 15 females) were fed fenitrothion at
0, 10, 30 and 150 ppm in the diet for 6 months. Growth, food and water
consumption, mortality, blood and urinalysis and blood biochemistry,
except cholinesterase activities, were comparable to the control in
all groups. The cholinesterase activities of the brain, red cells and
plasma were depressed in both sexes of the 150 ppm groups, but only in
the females of the 30 ppm groups and only in plasma of females in the
10 ppm group.
Absolute and relative organ weights were within normal limits,
except for slightly decreased relative weights of the spleen of males
of the higher dosage groups. No histopathological changes were found
in the examined organs including the spleen (Anon., 1972).
Dog
A toxicity study on the dog was composed of 3 sections: a 90-day
section for the purpose of range finding utilized an untreated control
group and three test groups, each consisting of eight purebred beagle
dogs (four males and four females) (Lindberg et al., 1972); the
one-year section utilized an untreated control group and two test
groups, each consisting of eight purebred beagle dogs (four males and
four females); and the two-year section utilized an untreated control
group and three test groups, each consisting of twelve purebred beagle
dogs (six males and six females) (Burtner et al., 1974). The one-year
and the two-year studies are summarized below:
As part of a one-year feeding, test groups of 4 male and 4 female
dogs were fed fenitrothion 0, 5 or 10 ppm in the diet for 90 days and
cholinesterase activities were determined three times pre-test and on
days 21, 45 and 90. The activities in the red blood cells were normal
at all times whereas in the plasma the activities were decreased 20
and 25% respectively in the two test groups. The 10 ppm group was
terminated after 90 days and the 5 ppm group continued for a total of
one year. The same examinations (growth, food intake, mortality, blood
and urine analysis, organ weights, histopathology and plasma,
erythrocyte and brain cholinesterase) were performed as for the 90-day
feeding test. No difference in blood and brain cholinesterase
activities (maximum inhibition was less than 12%) was found between
test and control groups (Burtner et al., 1974).
Groups of dogs (6 males and 6 females) were fed fenitrothion 0,
30, 100 and 200 ppm in the diet for two years. The same examinations
were performed as for the 90-day feeding test. The only adverse effect
was reduction of the cholinesterase activities. Depression of plasma
cholinesterase activity was apparent in all groups, while erythrocyte
enzyme activity was unaffected in the 30 ppm group when group averages
of treated and control animals were compared. Brain activity was
decreased only after ingestion of 200 ppm (Burtner et al., 1974).
Cattle, sheep, pigs
Cattle and sheep were given 3 mg fenitrothion/kg/day for 90 and
60 days respectively and the cholinesterase activity in the plasma was
measured. The activity decreased in both species early in the test
period, but had fully recovered after 30 days. Pigs given a single
dose of 31 mg/kg showed the typical signs of cholinesterase
inhibition, but the symptoms disappeared within 48 hours (Anon.,
1966).
Long-term studies
Rat
Groups of rats (15 males and 15 females) were fed diets
containing 0, 2.5, 5 and 10 ppm fenitrothion for 92 weeks. The
cholinesterase activity in the blood was studied and group averages
between treated and control groups compared after 2, 4, 6, 8, 12, 16,
20 and 24 weeks. In the 5 ppm group a 20-25% decrease in plasma
activity of males was seen during the first 16 weeks and a 20-35%
decrease in the females during 12 weeks. The activity recovered,
however, during the remaining test period. In the 10 ppm group the
plasma activity decreased during the first 8 weeks with 30-40% in the
males and 40-50% in the females. The activity gradually returned to
normal during the next 8 weeks. The activity of the red blood cells
was decreased 20-30% in both sexes during the first 6 weeks and then
fully recovered. Brain activity determined at the end of the test
period was not affected at any dose level (Kadota et al., 1974b).
Three groups of rats (50 males and 50 females) were fed
fenitrothion 10, 30, and 100 ppm in the diet for a period of 104
weeks. Sixty males and 60 females served as controls. These animals
were the F1a-generation from the previously mentioned reproduction
study (Rutter and Voelker, 1974b). Ten rats of each sex and group were
sacrificed after one year and all the surviving animals at 104 weeks.
Blood and urinalysis were performed several times during the test
period. Body weights of the high level males and females were lower
than the controls from the start of the test and remained so in males
until after the 52nd week, but at the end of the test no significant
differences were seen. Food consumption at 52 weeks was lower for the
middle and high level males, but normal for low level males and all
the females. In analysis of the mortality data of dosed groups
compared to controls no difference was found in female animals while
in males the mortality was significantly higher than the control in
the lowest dose group. The middle and high dose levels did not show
any difference from the control mortality. Blood and urine analyses
were normal except for cholinesterase activity which showed a
dose-dependent decrease. Significant depression occurred in plasma at
all 3 dosage levels, but in erythrocyte and brain only at the 100 ppm
level of both sexes. Statistical analysis of the probabilities of
tumour incidence (i.e. tumour incidence-adjusted-based on the number
of animals actually at risk in each group and sex) revealed no
difference between the control and the 10 ppm or 100 ppm level
animals. There was a decrease in the probability of only benign
tumours for the 30 ppm males and an increase of the probability of
pituitary adenoma incidence for the 30 ppm females, but since this was
not observed at 100 ppm it did not appear to be dose-related. Absolute
and relative organ weights and gross and histopathology revealed no
dose-dependent changes (Rutter and Nelson, 1974a).
Observations in man
Adult volunteers were divided into a control group consisting of
two men and two women and a test group of five men and five women. The
test period was divided into three parts with increasing dose levels,
followed by a recovery period. For some of the volunteers, this was
followed by a fourth test period. The volunteers were given
fenitrothion orally by gelatine capsules. The daily dose was divided
in three portions. Dosages were 0.1 mg/kg body weight and 0.3 mg/kg,
each for 21 days followed by 0.5 mg/kg for 3 days, then 18 days
recovery and finally 0.2 mg/kg for 21 days. Only 3 persons of the
control group and 5 of the test group continued after the recovery
period. Plasma and erythrocyte cholinesterase activity was determined
5 times prior to the test, 5 times during each of the 21 days test
periods, 3 times during the recovery period and on day 1 and 3 of the
short test period. Haematology was performed on the last day of the
long test and the recovery periods. Two of the persons had a
significantly depressed plasma cholinesterase activity (10-23%)
following the dosing with 0.3 mg/kg and the depression was increased
to 15 and 33% respectively at the 0.5 mg/kg does level. A third person
showed a 19%, significant, depression at this dose level. The
erythrocyte cholinesterase activity and the results of haematology
were within normal limits at all dose levels. Clinical symptoms
typical of anticholinesterase activity (nausea, abdominal cramps and
diarrhoea) were observed in approximately half of the dosed persons at
the 0.3 and 0.5 mg/kg level. No symptoms of cholinesterase inhibition
were noted with 0.2 mg/kg for 21 days (Garofalo et al., 1972).
COMMENTS
Studies of the S-methyl isomer, which occurs as an impurity in
technical fenitrothion, indicated that it is a much more potent
anticholinesterase agent but is more rapidly metabolized than the
parent compound. Acute and short-term studies on a major metabolite in
plants and animals, 3-methyl-4-nitrophenol (p-nitro-m-cresol),
indicated a low order of toxicity. Results of studies on delayed
neurotoxicity of fenitrothion in hens were negative. Results for tests
for mutagenicity were negative. Results of tests for teratogenesis and
two reproduction studies in rats indicated no adverse effects at doses
below those toxic to parents. Short-term studies in rats and dogs
showed that a depression of plasma cholinesterase was the most
sensitive indicator of effects and was considerably more sensitive
than brain cholinesterase inhibition. A 2-year feeding study in rats
was performed on the F1-animals from one of the reproduction studies.
Cholinesterase inhibition was the only dose-related effect observed in
human volunteers given fenitrothion and indicated that a dose of 0.2
mg/kg bw daily for 3 weeks did not produce inhibition of plasma or
erythrocyte cholinesterase nor cholinergic symptoms. Studies of tumour
incidence did not indicate a carcinogenic action. Because clinical
signs were noted without cholinesterase depression at a dosage of 0.3
mg/kg, the results of these studies were interpreted with caution in
estimating the ADI. Nevertheless, since the results of several studies
in animals have become available, the meeting allocated an ADI.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 5 ppm in the diet, equivalent to 0.25 mg/kg bw.
Dog: 5 ppm in the diet, equivalent to 0.125 mg/kg bw.
ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN
0 - 0.005 mg/kg bw.
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERN
The wide spectrum of activity against insects and the relatively
low toxicity towards mammals has resulted in a greatly increased field
of use against pests of agriculture.
Pre-harvest treatments
Many pre-harvest treatments have been approved in 35 different
countries. The recommended dosages in terms of active ingredient or
concentration of sprays for the major crops are listed in Table 5.
TABLE 5. Recommended dosages in terms of active ingredient or
concentration of sprays for the major crops.
Crop Recommended dosage
Rice 0.3 - 1 kg/ha
3-5 times/season
Wheat, barley 0.5 - 1 kg/ha
1-2 times/season
Pome and stone fruit 0.05 - 0.125%
3-5 times/season
Grapes 0.05 - 0.075%
2-3 times/season
Vegetables 0.1 - 0.5 kg/ha
2-3 times/season
Cotton 0.5 - 2 kg/ha
5-6 times/season
Coffee 0.5 - 0.7 kg/ha
2-3 times/season
Pasture 0.25 - 0.5 kg/ha
1-3 times/season
Post-harvest treatments
Most insects which attack stored products such as rice, wheat,
barley, oats, maize and oil seeds are susceptible to fenitrothion
(Green and Tyler, 1965; Kane and Green, 1968; Kashi, 1972). In
Australia, Brazil, India and Zambia the use of fenitrothion for the
treatment of grain storage structures and for application to the
outside of bagged products is approved.
Fenitrothion is under evaluation by the FAO Working Party of
Experts on Pest Resistance to Pesticides for stored grain use. The
Meeting had available extensive data from Australia where many large
scale trials as well as laboratory experiments have been carried out
to evaluate fenitrothion for addition to stored grain. The rate of
admixture effective against the major pests is 8-10 ppm.
Non-crop uses
Fenitrothion is extensively used for the control of forest
insects at the rate of 0.2-0.6 kg/ha. It is also used for the control
of bark beetles and weevils on logs and timbers at the rate of 1.5-3
g/m2.
One of the most important uses for fenitrothion is for the
control of locusts and grasshoppers where application is made by
ground equipment and aircraft at the rate of 0.3-0.5 kg/ha. Numerous
other insect pests of pastures and forage crops are presently being
controlled with fenitrothion where previously organochlorine
insecticides were used.
Other Uses
Fenitrothion is used extensively for the control of insects of
public health importance. One of the most extensive uses being the
control of mosquito vectors of malaria. For uses other than in malaria
control application is made at rates ranging from 0.2-1 g/m2. For the
control of the malaria mosquito application is made at the rate of 2
g/m2 (Sumitomo, 1974).
RESIDUES RESULTING FROM SUPERVISED TRIALS
Extensive new data were available from supervised residue trials
carried out on a wide variety of fruit and vegetable crops in Japan.
These are presented in Table 6 (Sumitomo, 1974).
Residue studies carried out on selected crops in Germany are
given in Table 7 (Bayer, 1972).
Residues in Rice
In response to one of the requirements of the 1969 Joint Meeting
extensive studies have been carried out in Japan to determine the
residue levels of fenitrothion in the grain of rice following approved
treatments. Over 120 samples of rice harvested following the
application of varying rates of fenitrothion (0.5-1 kg/ha) applied at
varying time intervals before harvest were analysed (Sumitomo, 1974)
by methods described by Takimoto et al. (1974). The data obtained from
the different applications are given in Table 6a. The average residue
TABLE 6. (Part I) Residues resulting from supervised trials in Japan (at intervals of 1-15 days)
Application No.
Rate, % or of Residue, mg/kg at interval (days) after application
Crop No. kg a.i./ha Formulation trials 1 3-4 7 9-11 13-15
Onion 1 0.05% EC 1 n.d.1 n.d.
Potato 3 or 6 0.5 or 0.75 EC 2 n.d.-0.004 n.d.-0.002 n.d.
kg/ha
Spanish 1 0.75 kg/ha EC 1 0.2 0.09 0.008 0.005 0.004
Paprika
Japanese Pear 3 or 6 0.04% WP 2 0.06-0.08 0.02-0.03
Peer 3 or 5 2.5 kg/ha WP 2 0.01-0.08 n.d-0.006
Egg plant 3 or 6 0.75-1.5 EC 0.001-0.01 n.d.-0.006 n.d.-0.002
kg/ha
Peach (pulp) 3 or 6 2 or 2.5 EC 4 0.07-0.08 0.03-0.07 0.005-0.015
kg/ha
Peach (peel) 3 or 6 2 kg/ha EC 2 2.2-2.9 1.1-1.6 0.3-0.6
Peach (peel) 3 or 6 2.5 kg/ha EC 2 5-5-6.1 5.5-6.2 1.8-2.1
Orange 1 2.25 kg/ha EC 4 n.d.-0.1
Grape 3 or 6 1 or 1.25 EC 4 1.1-2.8 0.5-1.1 0.1-0.9
kg/ha
Stone-leek 2 or 4 0.57 kg/ha EC 2 0.006-0.01 0.003-0.005 n.d.-0.001 n.d.
Stone-leek 2 or 4 2.86 kg/ha EC 2 0.09-0.2 0.09-0.2 0.09-0.2 0.02-0.03
TABLE 6. (Part I) (Cont'd.)
Application No.
Rate, % or of Residue, mg/kg at interval (days) after application
Crop No. kg a.i./ha Formulation trials 1 3-4 7 9-11 13-15
Strawberry 2 or 4 0.5 kg/ha EC 2 0.7-1.1 0-1-0.3 0.06-0.09
Strawberry 2 or 3 1.0 kg/ha EC 2 0.04-0.06 0.02-0.03 0.005-0.007
Soybean 2 or 3 0.71 kg/ha EC 4 0.02-0.03 0.02-0.05 0.001-0.002 0.001-0.01
Tomato 3 or 6 1.0 kg/ha EC 4 0.09-0.2 0.02-0.05
Tomato 3 or 6 2.5 kg/ha EC 4 1.3-2.7 0.4-0.9
Apple 1 or 2 0.04 or 0.05% WP 3 0.2 0.1-0.3 0.03-0.06
Apple 1 or 3 0-05% EC 2 0.2
1 n.d. not detected
TABLE 6. (Part II) Residues resulting from supervised trials in Japan (at intervals of 21-64 days)
Application No.
Rate, % or of Residue, mg/kg at interval (days) after application
Crop No. kg a.i./ha Formulation trials 21 28-32 34-36 41-49 51-64
Onion 1 0.05% EC 1 n.d.*
Rice 1 0.75 kg/ha EC 4 0.002-0.06 0.002-0.09 0.004-0.06
Rice 2 or 4 1.2 kg/ha MG** 4 n.d. n.d.
Orange 1 2.25 kg/ha EC 4 n.d.-0.009
Soybean 2 or 3 0.71 kg/ha EC 4 0.002 0.001-0.005
Apple 3 or 5 0.05% WP 2 0.001
Apple 1 or 3 0.05% EC 2 0.04 0.002
* n.d. = not detected
** MG = micro-granules
TABLE 6a. Residues of fenitrothion in rice grain following
standard treatments
Days No. of Residue of Sumithion
after samples (mg/kg)
Formulation application analysed Range Average
EC 11-20 14 0.303-0.012 0.109
21-40 15 0.154-0.003 0.051
41-67 18 0.005-0.001 0.001
Dusts 11-20 9 0.035-0.001 0.016
21-40 22 0.032-0.001 0.003
41-67 28 0.003-0.001 0.001
WP 11-20 4 0.060-0.022 0.036
21-40 8 0.059-0.001 0.020
41-67 8 0.001 0.001
level found ranges from negligible (0.001 mg/kg) to 0.1 mg/kg. From
these data, it is concluded that:
(1) regardless of post-treatment period, the residual amount of
fenitrothion was influenced by formulation. The residue remaining
after the use of emulsifiable concentrates is higher than that
from the use of wettable powders which in turn is higher than
that from the use of dusts.
(2) the maximum residue obtained 11-20 days after the final
application was 0.3 mg/kg. The average residue level was 0.11
mg/kg in the case of EC formulations. The residue level decreased
uniformly in the period between final application and harvest.
(3) 41-67 days after the final application, the residue was on an
average 0.001 mg/kg in the 54 samples (Sumitomo, 1969).
These data are in close agreement with the studies (Miyamoto and Sato,
1965) considered by the 1969 Joint Meeting (FAO/WHO, 1970).
TABLE 7. Residue levels in supervised trials - Germany
Rate Fenitrothion, mg/kg, after interval (days)
Crop kg/ha 0 1 7 10 14 21 50 90
Savoy cabbage 0.4 8.1 1.35 0.05 0.01 0.01
0.25 1.6 1.02 0.02 0.01 0.01
Wine grapes 0.88 9.5 4.5 0.8 0.7 0.7
Must 0.05
Wine grapes 0.88 8.8 1.5 0.27 0.15 0.1
Must 0.01
Grapes 0.625 0.01
Must 0.01
Wine 0.01
Grapes 0.025
Must 0.625 0.01
Wine 0.01
Miyamoto et al. (1965) studied the fate of 32P-labelled fenitrothion
applied to field-grown rice plants and found a very rapid decrease in
fenitrothion deposits.
3-methyl-4-nitrophenol residues were determined in harvested rice
grains following the application of fenitrothion. Using the Aich-asahi
variety, 0.36 mg/kg of 3-methyl-4-nitrophenol was found in rice bran
and negligible amounts in polished rice. This finding is consistent
with that reported by Hosokawa, and Miyamoto (1974) using
14C-labelled fenitrothion applied to apples hanging on the tree.
Post-harvest treatments
Green and Tyler (1965) demonstrated that when fenitrothion was
added to stored barley it gave a much more durable deposit and was
more effective than over 8 times the quantity of malathion. Dichlorvos
was relatively transient. In one experiment 0.54 mg/kg fenitrothion
added to barley declined only slightly, to 0.33 mg/kg, in 19 weeks. At
the end of the first six weeks the concentration found by analysis was
substantially the same as that at the time of treatment.
The Cooper Technical Bureau (1968) reports a series of 10
large-scale field trials in which fenitrothion was added to bulk wheat
stored in a variety of silos ranging in size from 6 tons to 6,000
tons. Details of the application rate and the residue levels found by
analysis at the beginning and end of the storage period are given in
Table 8.
Bengston et al. (1974) report the results of two large-scale
experiments where fenitrothion was applied to large bulks of wheat at
two different centres in Australia. Samples were taken in a
pre-determined pattern from various depths within the bulk of grain at
regular intervals after treatment. The temperature of the grain
remained approximately 30°C throughout the storage period. Samples
drawn at each stage of the experiment were analysed independently by
five separate laboratories. Bioassays against 16 strains of stored
product pests were carried out simultaneously on identical samples of
grain. The results of the chemical analyses are recorded in Table 9.
By comparison with malathion, fenitrothion deposits remained stable
over a much longer period and appeared to be less affected by storage
conditions.
The Sumitomo Chemical Company (1974) reports interim results of a
study of the persistence of fenitrothion on stored rice grain.
Unpolished rice was treated with diluted fenitrothion emulsion to give
concentrations of 2, 6 and 15 mg/kg of fenitrothion. The rice was
stored in kraft paper bags at 25°C for periods up to 6 months.
Moisture content of the grain during the experimental period was
between 13.1% and 14.1%. Results are given in Table 10.
TABLE 8. Fenitrothion as a grain protectant, summary of field trials (Australia)
Residues (mg/kg)
Storage Initial Final
Duration Formulation Application assay assay
State Capacity and type (months) type rate (Average) (Average) Observations
NSW 500-bushel galvanised 10 wmc 2.5 2.0 1.5 Protection maintained
iron silos 5.0 4.1 4.1 throughout trial
NSW 2,000-bushel galvanized 4 powder 2.5 1.0 0.1 Trial terminated by sale
iron silos - 5.0 2.2 ? of grain: inconclusive
'Farm treatment'
SA 2,000-bushel galvanised 9 powder 2.5 1.3 0.2 Protection maintained;
iron silos 5.0 2.8 0.4 data incomplete
NSW 7,000-bushel vertical 19 wmc 2.5 2.3 0.7 Protection maintained
concrete silo bins 10 2.5 2.3 0.7 throughout; surfaces
19 5.0 2.2 0.7 dusted with malathion
10 5.0 2.3 1.2 (20-25 ppm) at 8 months
NSW 32,000-bushel vertical 7 wmc 6.0 3.2 0.9 Protection maintained
concrete silo bins 3.2 0.9 throughout
9 wmc 6.0 3.2 1.0
3.8 0.8
WA 20,000-bushel vertical 10 3/4 wmc 6.0 3.5 0.8 Protection maintained
concrete silo bins throughout
NSW 200-bushel silo 6 wmc 6.0 3.4 1.8 Protection failed:
Rhizopertha dominica
surviving at 3 months,
infestation by 6 months
TABLE 8. (Cont'd.)
Residues (mg/kg)
Storage Initial Final
Duration Formulation Application assay assay
State Capacity and type (months) type rate (Average) (Average) Observations
NSW 250,000-bushel bulk 8 1/2 wmc 10.0 4.7 2.2 Protection maintained:
wheat Depot 1 spot infestation could
have been fumigated.
WA 20,000-bushel vertical 8 wmc 6.0 4.1 1.5 Protection maintained.
concrete silo bin
WA 47,000-bushel bulk 6 wmc 6.0 2.4 0.8 Final details awaited.
wheat depot Treated grain, processed
and assessed by Aust.
Bread Res. Inst., free
of taint or odour in
flour or bread.
TABLE 9a. Fenitrothion residues, mg/kg, in wheat from Site M
of two trials in Australia. Samples taken at various
depths analysed by independent laboratories.*
Sample Analyst
Since
Depth M. Treatment A B C D Mean
0.1 1 week 6.0 6.6 6.3
1.5 6.5 7.6 7.1
6.0 7.0 6.6 6.8
Mean 6.5 6.9 6.7
0.1 6 weeks 4.9 4.5 4.3 6.3 5.0
1.5 4.8 4.7 4.0 3.6 4.1
6.0 4.9 4.6 4.0 4.5 4.5
Mean 4.9 4.6 4.1 4.6 4.5
0.1 11 weeks 3.4 4.1 4.7 3.2 3.9
1.5 3.6 4.0 4.8 3.0 3.8
6.0 3.6 3.7 4.5 2.9 3.7
Mean 3.5 3.9 4.7 3.0 3.8
0.1 16 weeks 3.0 - - 3.3 3.2
1.5 2.8 - - 3.0 2.9
6.0 2.8 - - 3.1 2.9
Mean 2.9 - - 3.1 3.0
0.1 22 weeks 3.3 3.1 3.0 3.0 3.1
1.5 3.0 3.1 2.0 4.0 3.2
6.0 2.4 2.6 2.2 2.8 2.5
Mean 2.9 2.9 2.7 3.3 3.0
0.1 26 weeks - 2.2 3.4 -
1.5 - 2.2 3.0 -
6.0 - 1.6 2.1 -
Mean - 2.0 2.8 -
* Amount applied equivalent to 6 ppm on weight of wheat
(Approximately 1000 tonnes)
TABLE 9b. Fenitrothion residues, mg/kg, in wheat from Site W
of two trials in Australia. Samples taken at various
depths analysed by independent laboratories.*
Sample Analyst
Since
Depth M. Treatment A B C D Mean
0.1 2 weeks 4.8 4.5 4.0 4.2 4.3
1.5 4.4 4.1 - 4.6 4.4
6.0 4.8 5.0 4.2 5.6 5.0
Mean 4.7 4.5 - 4.8 4.7
0.1 8 weeks 4.5 4.5 5.8 5.5 5.0
1.5 3.6 3.8 4.9 4.1 4.0
6.0 3.8 4.3 5.3 4.8 4.5
Mean 4.0 4.2 5.3 4.9 4.5
0.1 13 weeks 4.5 6.1 8.0 6.2
1.5 4.6 5.4 7.4 5.8
6.0 5.0 6.5 4.1 5.2
Mean 4.7 6.0 6.5 5.7
TRIAL TERMINATED BECAUSE OF INFESTATION WITH RHIZOPERTHA DOMINICA.
TABLE 10. Residue of fenitrothion in/on unpolished and polished
rice and rice bran
Treatment Fenitrothion, mg/kg, after storing period (months)
dose,
Commodity mg/kg Initial 1 2 3 6
Unpolished 2 1.03 0.83 0.79 0.78 0.68
rice
6 3.92 2.82 2.68 2.44 2.18
15 9.38 6.54 6.09 5.85 5.45
control <0.01 <0.01 <0.01 <0.01 0.01
Polished Rice 2 0.13 0.12 0.11 0.09 0.09
6 0.44 0.32 0.29 0.25 0.26
15 1.02 0.83 0.67 0.58 0.58
control <0.01 <0.01 <0.01 <0.01 <0.01
Rice Bran 2 8.31 6.41 5.31 4.63 4.46
6 27.2 19.5 18.1 17.5 13.1
15 65.0 48.1 41.0 41.6 34.8
control 0.07 0.13 0.02 0.02 0.02
Although recovery studies indicated that close to 100% of a
measured amount of fenitrothion would be recovered from treated rice
grains, analysis of the samples prepared in the above experiment
recovered only from 43-53% of the amount of fenitrothion applied.
Irrespective of the amount applied (2, 6 and 15 ppm) the amount of
fenitrothion recoverable by analysis at the end of 6 months was only
about half that recovered immediately following treatment. The
greatest decline occurred in the first month and thereafter the
residues appeared to decline relatively slowly.
FATE OF RESIDUES
General Comments
Since the previous evaluation (FAO/WHO, 1970) some new
experimental work concerning the fate of residues has been reported.
The behaviour of fenitrothion in the environmental system, like that
of other pesticides which contain a nitrophenol moiety, is determined
by its readiness to form an aminophenol moiety by reduction of the
nitro group as well as by its transformation by hydrolysis. The
reduced compound has been found in polluted water, soil, animals,
plants and even following photodecomposition (Sumitomo, 1974).
In animals
Orally administered 32P-labelled fenitrothion was readily
absorbed from the digestive tract of guinea pigs or rats and the major
portion of the radioactivity was excreted in the urine. Neither
fenitrothion nor fenitrooxon was detected and desmethyl fenitrothion,
dimethyl phosphorothionate and dimethyl phosphate were eliminated in
the urine (Miyamoto et al., 1963). Following intravenous injection of
radioactive 32P-fenitrothion into guinea pigs and rats fenitrothion
rapidly disappeared from the blood. Fenitrothion and fenitrooxon were
found in tissues and their amounts decreased rapidly. The desmethyl
compound and the dimethyl esters mentioned above were found mostly in
the liver and kidneys (Miyamoto, 1964).
Details of metabolic studies in animals are given in the 1969
monograph (FAO/WHO, 1970) where an outline of the degradation pathway
is shown. Excretion of metabolic products is rapid and chiefly in the
form of 3-methyl-4-nitrophenol, the fenitrothion hydrolysis product
(Hladka and Nosil, 1967).
Thirty calves (1-1.5 years, average weight 243 kg) confined on a
pasture sprayed with 375 g/ha, of fenitrothion (11.8 mg/kg initial
residue on the grass) were periodically sacrificed and muscle and
omental fat were analysed. On the first day residues in the meat and
fat were about 0.01 mg/kg. No residue of fenitrothion was found in the
meat from the third day onwards and only 0.004-0.007 mg/kg was found
in the fat on the third day. These amounts decreased almost to control
levels by the seventh day (Anonymous, 1968; Miyamoto and Sato, 1969).
Lactating dairy cows were fed 50 ppm of fenitrothion in the feed
(dry basis) for 29 days. No residue of fenitrothion, fenitrooxon, or
the cresol appeared in the milk. A maximum of 0.006 mg/kg of
amino-fenitrothion was found (Bowman, 1969).
Silage prepared from corn treated with 1, 2 and 3 kg/ha of
fenitrothion was fed to lactating Jersey cows for 8 weeks. Although
traces (0.001-0.005 mg/kg) of amino-fenitrothion were found in the
milk of cows fed the 3 kg/ha silage, no residues (less than 0.001
mg/kg) were found in the milk of cows consuming silage treated at
lower levels (Leuck et al., 1971). The urine contained total
metabolites averaging from 0.53-5.1 mg/kg but these consisted mostly
of amino-fenitrothion and about 0.1 mg/kg or less of the parent
insecticide and its cresol. Although faeces of the cows contained low
levels of residue (0.04-0.18 mg/kg, mainly as the amino compound)
neither blood cholinesterase depreciation nor any abnormality of
general health or milk production were noted.
Jersey cows were fed on diets spiked with 0, 25, 50 and 100 ppm
of fenitrothion for 28 days. Consumption of diets containing
fenitrothion did not depress feed intake, milk production or blood
cholinesterase activity. Milk, urine, and faeces from cows fed as much
as 100 ppm dietary fenitrothion contained neither fenitrothion, its
oxygen analogue, nor its cresol; but the amino analogue of
fenitrothion in milk, urine and faeces of cows fed the 25, 50 and 100
ppm diets averaged 0.002-0.17, 4.64-35.6, and 0.19-1.80 mg/kg
respectively. Seven days after feeding the diets containing
fenitrothion was terminated, residues could not be detected in milk,
urine, or faeces from any cows (Johnson and Bowman, 1972).
In plants
Apples hanging on the tree were dipped in a 0.1% emulsion of 14C
labelled fenitrothion and maintained under natural weather conditions.
The half-life of the parent compound in and on fruit was found to
range between 1 and 3 days, and fenitrooxon, fenitrothion S-isomer,
p-nitrocresol and desmethylfenitrothion were found.
p-nitrocresol-ß-glucoside was also found and it was concluded
that the absorbed fenitrothion was gradually hydrolysed to
p-nitrocresol in the tissues and that it was conjugated with glucose
(Hosokawa and Miyamoto, 1974).
Coastal bermuda grass and corn treated with an emulsifiable
concentrate of fenitrothion at 1, 2 and 3 kg/ha and sampled at 0, 1,
7, 14, 21 and 28 days post-treatment were analysed for residues of the
parent compound, its oxygen analogue and its cresol. The residues of
the parent compound diminished rapidly, those of the O-analogue were
low (none were detected in the 21 and 28 day samples), and those of
the cresol were highest in the 1 and 7-day samples. The total residue
on both crops diminished to less than 1 mg/kg in 28 days. In contrast,
residues of the parent compound and its O-analogue in corn ensiled in
glass jars were relatively stable and diminished at a much lower rate,
and the residues of the cresol increased significantly (Leuck and
Bowman, 1969).
In water
Fenitrothion was found to be very stable under sterile acidic
conditions at 37°C, while under alkaline conditions it was hydrolysed
rapidly with a half-life of three days at pH 11 and less than 24 hours
at pH 13, forming only 3-methyl-4-nitrocresol. Other decomposition
products were hardly observed at these alkaline pH's, while under
neutral and acidic conditions trace amounts (at most 2% of the initial
radio-activity) of unidentified compounds were formed (Miyamoto,
1974).
The fate of fenitrothion in river water with sediment was
demonstrated by using actual river water containing 2.5, 5 and 10 mg/l
of fenitrothion. The half-life was approximately 50 hours in aerated
samples and 30-40 hours in non-aerated samples where decomposition was
accelerated by anaerobic bacteria (Zitko et al., 1974).
In soil
Decomposition and leaching of fenitrothion in 4 different types
of soil were studied under laboratory conditions (Miyamoto, 1974a).
Carbon-14 labelled fenitrothion at 10 ppm was added to two kinds of
silty loam, sandy loam and sand, and kept at 25°C in the dark under
upland or submerged conditions. Under upland conditions fenitrothion
was decomposed with a half-life of 12-28 days depending on the type of
soil. The major decomposition products were 3-methyl-4-nitrophenol and
carbon dioxide. 3-methyl-4-nitrophenol, formed during the early period
of the incubation, amounted to 10-20% while the amount of carbon
dioxide reached approximately 40% after 60 day incubation in the silty
loam and the sandy soil.
Under submerged conditions decomposition of fenitrothion was even
more rapid than in upland conditions and amino-fenitrothion, the major
metabolite, was produced quite rapidly; in the silty and sandy loam
50-70% of the fenitrothion was converted to amino-fenitrothion in
approximately 10 days. Since fenitrothion was stable in sterilised
soil, micro-organisms might play a major role in the decomposition,
fungi being likely to be more active than bacteria. In the leaching
study, fenitrothion and its radioactive decomposition products were
not significantly eluted from 3 types of soil and remained at or near
the top. Only in sand with low organic matter and clay content, were
these compounds loosely bound to the soil allowing them to migrate
easily with moving water.
In storage and processing
Fenitrothion applied to unpolished rice (post-harvest application
for grain protection) at rates of 2, 6 and 15 mg/kg resulted in 0.68,
2.18 and 5.45 mg/kg respectively remaining after 6 months of storage
at 25°C. At the highest dosage rate, 15 mg/kg applied to rice grain
decreased to 6.54, 5.85 and 5.45 mg/kg, after 1, 3 and 6 months
storage respectively. Details of the distribution of fenitrothion
residues on unpolished and polished rice and rice bran are given in
Table 10 (Sumitomo, 1974).
Bengston et al. (1974) as part of an extensive evaluation of
grain protectants in Australia, submitted grain which had been treated
with fenitrothion 13 and 26 weeks previously to a laboratory scale
milling and baking trial. The distribution of fenitrothion residues in
the raw grain, milled grain products and bread is given in Table 11.
It will be noted that there is a minor discrepancy between the results
of 2 participating laboratories, one of which reports no residues in
bread, the other reporting residues at the limit of determination.
TABLE 11. Fate of fenitrothion residues in wheat subjected to milling and baking1
Fenitrothion, mg/kg
Wheat W Wheat M
Stage of Laboratory A Laboratory B Laboratory B
Processing 1 2 Mean 1 2 Mean 1 2 Mean
Whole grain 4.0 3.9 4.0 4.2 4.0 4.1 3.0 3.1 3.0
Cleaned grain 3.2 3.2 3.2 - - - - - -
Bran 9.4 11.3 10.4 8.0 8.6 8.3 8.2 8.0 8.1
Shorts (pollard) 8.0 7.6 7.8 6.1 6.1 6.1 6.2 5.8 6.0
Flour 0.44 0.47 0.5 0.35 0.3 0.3 0.66 0.68 0.6
Bread 0.11 0.11 0.1 ND2 ND ND T3 T T
<0.2 <0.2 (0.1) (0.1) (0.1)
1 From wheat in trials referred to in Table 9.
2 ND = not detected.
3 T = trace.
Photodecomposition
An extensive study of the fate of fenitrothion under the
influence of ultra-violet light has been performed by Ohkawa et al.
(1974). Irradiation of fenitrothion in various solutions with UV light
in air resulted in rapid photodecomposition, depending upon the
solvent used, and the following compounds were produced:
carboxy-fenitrothion (the main decomposition product),
fenitrooxon, carboxy-fenitrooxon, 3-methyl-4-nitrophenol,
3-carboxy-4-nitrophenol and parathion-methyl.
Irradiation with UV light in nitrogen produced none of these products,
but a trace amount of fenitrothion S-isomer was found in aqueous
methanol. When fenitrothion was exposed to sunlight in water solution,
carboxy-fenitrothion was the main decomposition product and
fenitrooxon, 3-methyl-4-nitrophenol, 3-carboxy-4-nitrophenol and
fenitrothion S-isomer were also detected. When fenitrothion deposits
on silica gel chromatoplates were exposed to sunlight or UV light,
carboxy-fenitrothion and fenitrooxon were the major decomposition
products. Carboxy-fenitrooxon, 3-methyl-4-nitrophenol and
4-carboxy-4-nitrophenol were also obtained. When 14C-fenitrothion was
applied to surfaces the radio-carbon was more rapidly lost from the
leaf surfaces of bean plants than from silica gel chromatoplates, but
the same products in almost the same proportions were found on both
surfaces. Two major products, carboxy-fenitrothion and fenitrooxon,
and 3-methyl-4-nitrophenol were further degraded into more polar
products, and finally into polymeric humic acids. Certain carbamate
and pyrethroid insecticides slightly accelerated the
photodecomposition of fenitrothion.
METHODS OF RESIDUE ANALYSIS
Despite the large number of methods for the analysis of
fenitrothion, it was not until 1969 that a method capable of analysing
for fenitrothion, fenitrooxon and the cresol was reported (Bowman and
Beroza, 1969). This method has now been extended to include
S-methyl-fenitrothion (Hallett et al., 1974). Although fenitrothion
can be readily separated from fenitrooxon and S-methyl-fenitrothion by
GLC it is more convenient and accurate to separate the phosphate
esters by column chromatography prior to GLC analysis (Bowman and
Beroza, 1969).
The solvent and the technique used to extract fenitrothion from
tissues are determined by the nature of the material to be analysed.
Materials with a high water content such as fruit and some vegetables
are blended with polar solvents: acetonitrile (McLeod et al., 1969;
Watts et al., 1969); acetone (Mollhoff, 1968) or methanol (Sumitomo,
1974). For materials containing both fat and water, e.g. milk and
meat, combinations of polar and non-polar solvents have been used:
methanol/acetronitrile (Miyamoto et al., 1967), chloroform/methanol
(Bowman and Beroza, 1969). For dry materials, e.g. rice and grain,
benzene has been used (Sumitomo, 1974). Non-polar solvents like hexane
are also used for materials with a high fat content, e.g. omental fat
(Miyamoto and Sato, 1969).
Gas-liquid chromatography is generally the method of choice for
the quantitation of fenitrothion and its metabolites. Although some
analyses for fenitrothion have been carried out using an electron
capture (EC) detector (Dawson et al., 1964; Kahazawa and Kawahara,
1966), current methods invariably use selective phosphorus detectors.
The sensitivity of the alkali flame ionization detector (AFID) to
phosphorus compounds is generally greater than that of the flame
photometric detector (FPD) by a factor 10-30. On the other hand, the
precision of the results obtained with an FPD is usually better.
Bowman and Beroza (1969) used the FPD whilst Miyamoto and Sato (1969)
and Hallett et al. (1974) have used the AFID. The response of
fenitrothion was found to be greater by a factor of 3 than that of
fenitrooxon and S-methyl-fenitrothion with an AFID. The least
detectable amounts are 8.6 x 10-13 g/sec for fenitrothion, 2.9 x 10-12
g/sec for fenitrooxon and 2.5 x 10-12 g/sec for S-methyl-fenitrothion
(Greenhalgh et al., 1974). The difference in sensitivity was
attributed partly to peak shape and partly to combustion conditions in
the flame. Although the sensitivity of detection of aminofenitrothion
with the AFID and the FPD is comparable to that of fenitrothion, it is
some 250 times less for an EC detector (Greenhalgh, 1974b).
Greenhalgh (1974a) reviews the information on various columns and
packing materials and as reported separately Greenhalgh (1974b) has
shown the advantage of using 4% SE-30/6% QF-1 on Chromosorb W. This
column readily resolves amino-fenitrothion, fenitrothion, fenitrooxon
and S-methyl-fenitrothion in that order. It is free from interference
from parathion and parathion-methyl.
Although it is possible to separate fenitrothion and its polar
metabolites by GLC, separation can also be achieved using liquid
column chromatography. Bowman and Beroza (1969) used de-activated
silica gel (20% H2O) to clean up extracts of corn and Bermuda grass
and at the same time separate fenitrothion, its cresol and
fenitrooxon. Activated Florisil has also been used to clean up
fenitrothion, with a recovery of 97% on elution with ether/benzene,
1:2 (Beckman and Garber, 1969). It has also been used to clean up
grain extracts containing fenitrothion (Horler, 1966). Bowman and
Beroza (1969) reported that alumina decomposed the fenitrothion.
A more detailed study has been carried out on the recovery of
fenitrothion and fenitrooxon at the 1.6 g level using silica gel,
Florisil and carbon columns (Hallett et al., 1974). All three columns
gave a 95-100% recovery of fenitrothion, which was eluted with
benzene. Further elution with acetone/benzene, 3:1, gave fenitrooxon.
The recovery of the fenitrooxon was, however, dependent on the
activity of the column as shown in Table 12.
TABLE 12. Recovery of fenitrooxon
% Water % Recovered
in packing Florisil Silica gel
0 0 100
5 50-58 100
10 100 100
15 100 64-66
25 100 64-69
The cresol was not studied because it did not interfere when
using specific phosphorus GLC detectors. The carbon column also gave
good recoveries of both fenitrothion and fenitrooxon (Watts et al.,
1969). This column is very useful for highly pigmented extracts but is
inconvenient to prepare.
The recoveries quoted for fenitrothion in Table 6 differ from the
results of Bowman and Beroza, (1969). This can be attributed to the
absence of large amounts of sodium sulphate and a different elution
pattern. It has since been found that Florisil will decompose
S-methyl-fenitrothion to some extent. Silica gel (2% H2O) is now
Preferred. A 95-100% recovery of fenitrothion, fenitrooxon and
S-methyl-fenitrothion is achieved at the 1 µg level. The S-methyl
isomer is eluted in the acetone fraction with the fenitrooxon.
Takimoto and Miyamoto (1974) have assembled the results of
extensive experience in the determination of fenitrothion residues
into a set of detailed procedures for handling a wide range of
different substrates. A series of extraction and clean-up procedures
are laid down for each different situation. Quantitation is attained
by GLC methods using the flame thermionic detector (FTD). For most
substrates the limit of determination is 0.005 mg/kg but according to
the authors it is often easy to determine fenitrothion at a level as
low as 0.001 mg/kg or even less.
Krehn (1973) has prepared an extensive review which includes
detailed information on residue analysis, confirmatory tests, cleanup
and quantitation.
NATIONAL TOLERANCES REPORTED TO THE MEETING
The following national tolerances were reported to the meeting.
TABLE 13. National tolerances reported to the Meeting
Tolerance
Count Crop mg/kg
Australia apples, cherries, grapes, 0.5
lettuce
red cabbage, tea (green) 0.3
tomatoes 0.2
cocoa 0.1
milk and milk products 0.05*
(fat basis)
meat and fat of meat 0.03*
Czechoslovakia fruits, vegetables 0.5
Germany (Federal vegetables 0.4
Republic of)
Holland cereals, fruits 0.5
Japan rice, soybeans, persimmon, 0.2
pear, apple, mandarin,
orange, peach, grapes,
strawberries, pumpkin,
cucumber, onion, tomato,
egg plant, green pepper,
lettuce, tea
Poland fruits, vegetables 0.4
APPRAISAL
The 1969 Joint Meeting after reviewing the available information
on fenitrothion specified that further work or information was
required on residue levels in commodities moving in commerce, on
disappearance during storage, on residue decline in rice, on
persistence of residues in stored grains, on occurrence of
4-nitro-3-methyl phenol, and on the quality of technical fenitrothion.
Evaluation of gas-chromatographic methods for regulatory purposes was
desirable.
The Meeting received considerable information on all these
questions with the exception of residues in commodities moving in
commerce. There was additional information on other uses, extensive
new data on the chemical, physical and biological properties of
fenitrothion and extensive information on new residue studies. While
new uses have been developed these have mainly been an extension to
other crops, the rate of application remaining similar to that
referred to in the 1969 Meeting.
There is a potential demand for fenitrothion as a grain
protectant and extensive data are available on the performance and
fate of fenitrothion in wheat and rice and in milled products from
these grains. The usefulness of fenitrothion for this purpose is
highlighted by the worldwide development of insect strains resistant
to malathion.
Results from the analysis of many different grades of technical
fenitrothion were considered by the Meeting and the significance of
the various components has been studied in relation to the fate of
fenitrothion in the environment in general and in many separate
aspects.
It was recognized that the residues on fruits, vegetables, forage
crops and pasture resulting from approved uses of fenitrothion were
relatively low and that their level declined rapidly with a half-life
of 1 to 2 days. There is no tendency for fenitrothion or its
metabolites to accumulate in animal tissues or foods of animal origin
following approved uses on pasture or forage crops or from feeding of
food-processing wastes.
The many methods of residue analysis have been examined and
reviewed by numerous authors. It is generally accepted that the method
of Bowman and Beroza (1969) is suitable for regulatory purposes,
particularly as it is capable of analysing for the parent fenitrothion
together with fenitrooxon and the residual cresol. Takimoto and
Miyamoto (1974) have documented procedures for dealing with many
substrates with corresponding extraction and clean-up procedures.
Quantitation is attained by GLC methods using flame thermionic and
electron capture detectors. The limit of determination is reported to
be 0.005 mg/kg in many substrates.
RECOMMENDATIONS
TOLERANCES
The following tolerances, which revise recommendations made in
1969, are recommended. The maximum residue limits include the parent
fenitrothion and the oxygen analogue fenitrooxon expressed as
fenitrothion (mg/kg).
Crop mg/kg
Wheat bran 20
Wheat 10
Wheat flour (wholemeal) 5
Peaches 2
Wheat flour (white) 1
Apples, cabbage, red cabbage, cherries, grapes,
lettuce, peas, rice (in husk), strawberries, tea
(green, dry), tomatoes 0.5
Leeks, oranges, radishes, bread (white) 0.2
Cauliflower, cocoa beans, egg plant, pears,
peppers, rice (polished), soybeans (dry) 0.1
Cucumbers, meat, fat of meat, milk, milk
products, onions, potatoes 0.05*
* At or about the limit of determination
FURTHER WORK OR INFORMATION
DESIRABLE
1. Further observations in man.
2. Results from studies now in hand on the effect of cooking on
fenitrothion residues in rice.
3. Further studies to determine the fate of residues during the
cooking of other cereal products from wheat and rye.
4. Information on the level and fate of residues following
post-harvest use on oats, barley and rye.
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