BROMOPHOS-ETHYL JMPR 1975
Explanation
In 1972 the Joint Meeting (FAO/WHO, 1973) evaluated bromophos-
ethyl in the light of the information then available. A temporary ADI
and some temporary tolerances were recommended.
The Meeting required residue data from supervised trials in
maize, rice and other cereals, cotton, domestic animals other than
cattle, and milk products. The Codex Committee on Pesticide Residues
at its 8th Session requested that a maximum residue limit for milk
products should be established (Alinorm 76/24, para. 46).
New information has been received on residues in maize, rape seed
and green rape resulting from supervised trials, on residues in the
tissues of dosed and dipped sheep and on residues in butter made from
the milk of dipped cows. This information is summarized in the
following monograph addendum.
Other information on identity and properties
Solubility: 2 mg/kg water (Eichler, 1972)
EVALUATION FOR ACCEPTABLE DAILY INTAKE
TOXICOLOGICAL STUDIES
Short-term studies
Rat
Groups of young rats (10 male and 10 female per group) were fed
bromophos-ethyl in the diet for four weeks at dose levels of 0 and 100
ppm. Behaviour and mortality were unaffected over this time interval.
Growth, evidenced by body weight changes, and food and water
consumption were normal. RBC cholinesterase activity was inhibited
(50%) within one week after treatment began. Normal activity was
almost reached one week after treatment ended. At the four week post
treatment interval, RBC activity was normal. Plasma cholinesterase
activity was inhibited similarly at one week after feeding began (app.
60%) and activity again recovered within one week after feeding
ceased. Cholinesterase depression was rapid but was not progressive.
The lowest levels of both plasma and RBC cholinesterase activity were
achieved in one week. Serum ascorbic acid levels, and urine ascorbic
acid and dehydroascorbic acids levels measured at 0, 1, 2, 4, 5 and 9
weeks after initiation of the study were normal at all time intervals.
There were no changes noted in ascorbic or dehydroascorbic acid levels
in serum or urine (Leuschner, 1975).
Guinea-pigs
Groups of guinea-pigs (10 males and 10 females/group) were fed
bromophos-ethyl in the diet for four weeks at dose levels of 0 and 100
ppm. The animals were maintained on control diets for a further four
week period to measure recovery from any effects noted. As in the
previous study, no adverse effects were noted on behaviour, food or
water consumption, growth or on mortality over the entire test period.
As noted with rats, plasma cholinesterase activity was depressed
within one week and maintained at a constant low (40% of normal) level
until the fourth week. After bromophos-ethyl was removed from the
diet, the plasma enzyme activity rapidly recovered within one week and
was normal after four weeks. In contrast to rats, the RBC
cholinesterase activity of guinea-pigs was not affected by
bromophos-ethyl at any time interval. Serum ascorbic acid levels and
urine ascorbic acid and dehydroascorbic acid levels, measured at 0, 1,
2, 4, 5 and 9 weeks after initiation of the study were normal. There
were no changes noted in ascorbic or dehydroascorbic acid levels in
serum or urine (Leuschner, 1975).
COMMENTS
Bromophos-ethyl was evaluated by a previous Meeting and a
temporary ADI was allocated.
Studies in rats and dogs showed an increase in urinary excretion
of ascorbic acid and dehydroascorbic acid in two year rat and dog
studies as well as shorter-term studies in both species. In an effort
to further define these effects and to evaluate its relevance to man,
short-term feeding studies in rats and guinea-pigs were repeated. The
previously noted increased ascorbic acid and dehydroascorbic acid
levels in urine were not seen in this study. In addition, blood levels
of these materials were not altered by bromophos-ethyl in the diet.
Cholinesterase depression was noted in both species attesting to the
presence of bromophos-ethyl in the diet.
The Meeting now considered the rat study to be complete and a
dietary no-effect level based on cholinesterase depression was
observed to be 0.78 mg/kg/day. A no-effect level in the dog was 0.26
mg/kg/day and was utilized as the basis for estimating the ADI.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effects
Rat: 0.78 mg/kg body weight/day
Dog: 10 ppm in the diet equivalent to 0.26 mg/kg body weight
ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN
0-0.003 mg/kg body weight
RESIDUES IN FOOD AND THEIR EVALUATION
RESIDUES RESULTING FROM SUPERVISED TRIALS
Maize
In four supervised trials in Germany and in the Netherlands,
maize was treated against the frit fly (Oscinella frit L.). In
May/June plants were sprayed with an EC at a rate of 0.54-0.57 kg
a.i./ha (normal application rate). Residues were determined by GLC
after pre-harvest intervals between 28 and 154 days. Maximum residues
of 0.05 mg/kg were found in the kernels 28 days after a single
application. In all other studies residues in maize plants or kernels
were at or below 0.02 mg/kg (limit of determination; Celamerck,
1975a).
Since two applications may be necessary to control strong
infestations of insect pests, corresponding residue data should be
supplied.
Rape
For the 1972 Joint Meeting Report only limited residue data for
rape seed after a single application of bromophos-ethyl (EC) were
available. Since rape is treated one to three times, additional data
have been supplied (Celamerck, 1975b), and are listed in Table 1.
Vegetables
Additional data on residues on carrots and Brussels sprouts have
been supplied (Table 1). The data on Brussels sprouts include residues
found at various stages of household preparation.
Sheep
A single dose of 25 mg bromophos-ethyl/kg body weight was
administered orally to a sheep weighing 33.6 kg (TVL, 1975). The
levels (mg/kg) in blood were 0.06 (one hour after dosing), 0.32 (three
hours) and 0.20 (five to seven hours).
After 72 hours the same sheep was again dosed with 25 mg/kg and
slaughtered 48 hours later. Maximum residues in organs and fat (two
samples each) were: muscle 1.0, liver 0.1, kidney 0.28, spleen <0.01,
brain 0.025, renal and omental fat 13, and back fat 5 mg/kg.
In another experiment (TVL, 1975) sheep (Romney Cheviot Crossbred
Hoggets) were dipped in washes containing 0.05% (normal strength) and
0.1% bromophos-ethyl. The amounts of bromophos-ethyl in the fat of
these sheep are listed in Table 2.
TABLE 1. Bromophos-ethyl residues in crops
Application
Residue (mg/kg) at interval (days) after application
kg
Crop No. a.i./ha 0 3-4 7 14 21 24-28 42 60 90
Brussels sprouts1,2 3 0.6 0.32- 0.26- 0.06- 0.07- 0.03- 0.16-
0.50 0.32 0.46 0.55 0.12 0.35
"2 4 0.6 0.05- 0.36- 0.26- 0.15-
0.52 0.63 0.46 0.25
"3 1 0.8 0.11- 0.11-
0.22 0.19
"4 1 0.8 0.03- 0.03-
0.10 0.05
"5 1 0.8 <0.04 <0.03
Carrots6 1 6 0.49-1.6 0.22-
0.24
Rape seed7 1 0.54 <0.02
" 2 0.43 <0.02 <0.02
" 4 0.36 0.35-
0.39
" 1 0.43 <0.02 0.03
(50 days) (56 days)
TABLE 1. (continued)
Application
Residue (mg/kg) at interval (days) after application
kg
Crop No. a.i./ha 0 3-4 7 14 21 24-28 42 60 90
Rape plants7 3 0.728 19.1 8.6 6.4 3.1 1.9
(green)
" 3 0.36 9.9 3.9 2.6 1.3 0.8
1 RIV, 1970
2 RIV, 1971b
3 Trimmed (other small leaves removed) RIV, 1974
4 After cleaning and washing, RIV, 1974
5 After cleaning, washing and cooking, RIV, 1974
6 RIV, 1971a
7 Celamerck, 1975b
8 Twice the normal dosage.
TABLE 2. Bromophos-ethyl residues in the fat of sheep after dipping
Bromophos-ethyl residues (mg/kg) in
Period between
dipping and % a.i.
sampling (days) in dip Back fat Renal fat Omental fat
2 0.05 0.6-1.1
0.1 0.7-3.1
7 0.05 1.0-3.4
0.1 1.5-2.9
14 0.05 0.9-1.9 1.5 1.2
0.1 0.6-2.5 1.9 2.8
28 0.05 0.3-0.4
0.1 0.4-1.0
42 0.05 0.03-0.14
0.1 0.03-0.3
56 0.05
0.1 0.02 0.10 0.04
Cows
After dipping four lactating dairy cows (Jersey) in a
concentration of 0.049% (w/v) bromophos-ethyl, milk samples were taken
from each of the cows, and the butter prepared from these samples was
analysed for residues (Wollongbar Agric. Res. Stat., 1969). Amounts of
bromophos-ethyl after various intervals following dipping were as
follows: 0.49-0.87 (mg/kg butter) at 0 days (after dipping), 0.87-1.13
at 1 day, 0.35-1.02 at 2 days, 0.24-0.47 at 3 days, 0.08-0.12 at 4
days, 0.06-0.08 at 5 days, 0.02-0.04 at 6-7 days and 0.01 or below at
8-17 days.
APPRAISAL
The 1972 Joint Meeting, after reviewing the information on
bromophos-ethyl, required residue data from supervised trials in
maize, rice and other cereals, cotton, domestic animals other than
cattle, and milk products before tolerances could be recommended. Some
of the required information has now been supplied. After a single
application and a pre-harvest interval of 28 days, maximum residues
were 0.05 mg/kg in maize kernels and 0.02 mg/kg in fresh maize plants
used for feed. Higher dosage and repeated application led to residues
of bromophos-ethyl up to 0.39 mg/kg in rape seed and 0.8 mg/kg in
green rape at 28 and 21 days respectively after the last treatment.
Further residue data have been supplied for carrots and Brussels
sprouts. In the case of Brussels sprouts, some data are also available
on residue levels after trimming, washing and cooking.
Experimental oral application of high doses of bromophos-ethyl to
a sheep led to high residues in body fat but considerably lower levels
in muscle, kidney, liver, brain and spleen. Fourteen days after
dipping sheep in washes containing 0.05% bromophos-ethyl, residues in
back, renal and omental fat were below 2 mg/kg.
The dipping of dairy cows at recommended rates resulted in a
maximum residue of 1.13 mg/kg in butter fat after one day. This fell
to 0.24-0.47 mg/kg after 3 days, 0.02-0.04 mg/kg after 6-7 days and
0.01 mg/kg or below after 8 days. Cows in one area are not treated
simultaneously, and it can be assumed that milk from a treated herd
will be diluted about fourfold or more with milk from untreated cows
(see also section 2.5 of the 1971 Joint Meeting Report, FAO/WHO,
1972). A maximum residue limit of 0.2 mg/kg for milk and milk products
(fat basis) should therefore be adequate (see also coumaphos,
Evaluations). Maximum residues in body fat amounted 0.24 mg/kg three
days after spraying.
Although same of the information required by the 1972 Joint
Meeting has been submitted further information which is listed below
is still desirable to enable tolerances to be recommended for further
commodities.
RECOMMENDATIONS
As an ADI has now been allocated, the previously recommended
temporary tolerances are confirmed as maximum residue limits, with the
exception of the limit for whole milk (previously 0.02 mg/kg) which is
deleted and replaced as shown below. The following additional maximum
residue limits, determined and expressed as bromophos-ethyl, are
recommended.
MAXIMUM RESIDUE LIMITS
Limit
Commodity (mg/kg)
Fat of meat of sheep 3
Milk and milk products (fat basis) 0.2
Maize (kernels and fodder) 0.05
FURTHER WORK OR INFORMATION
DESIRABLE (in addition to the information as listed in FAO/WHO,
1973a, p. 43)
1. Residue data from supervised trials on cereals other than
maize, on cotton and on fruit and vegetables after repeated
application where this forms a part of good agricultural
practice.
2. Further information on use patterns including data on rates,
frequencies of application, and pre-harvest intervals,
especially on black and red currants, peaches, strawberries,
blackberries or raspberries, Brussels sprouts, cauliflower,
kale, sugar beets and sugar beet tops, together with residue
data where appropriate.
3. Further information on the fate of residues in vegetables
after cooking, especially carrots and spinach.
REFERENCES
CCPR. (1975) Report of the 8th session of the Codex Committee on
Pesticide Residues, CL 1975/13; August 1975
Celamerck. (1975a) Bromophos-äthyl, Rückstandsdaten in Mais.
(Unpublished data sent to FAO)
Celamerck. (1975b) Bromophos-äthyl, Rückstandsdaten in Rape.
(Unpublished data sent to FAO)
Eichler, D. (1972) Bromophos and bromophos-ethyl residues. Residue
Reviews, 41:65-112. F. A. Gunther, Ed., Springer Verlag, New York -
Heidelberg - Berlin
Leuschner, F. (1975) The influence of bromophos-ethyl-batch 4/73
called "B-Athyl" on ascorbic acid values and cholinesterase activity
in rats and guinea pigs. Unpublished report from the Laboratorium für
Pharmakologie und Toxikologie, Hambourg, FRG, submitted to the World
Health Organization by Celamerck GmbH & Co. KG Ingelheim am Rhein
RIV. (1970) Rijksinstituut voor de Volksgesondheid, No. 27/70 Tox-RoB,
Residuen van bromofos-ethyl in spruitkool (maart 1970)
RIV. (1971a) Rijksinst. v.d. Volksgezondheid, No. 86/71 Tox-RoB,
Bestrijding van weitelvlieg met bromofos-ethyl (juni 1971)
RIV. (1971b) Rijksinst. v.d. Volksgezondheid, No. 125/71 Tox-RoB,
Residuen van enige orjanofosfor insekticiden in spruitkool (august
1971)
RIV. (1974) Rijksinst. v.d. Volksgezondheid, No. 61/74 Tox-RoB,
Residuen van bestrijdingsmiddelen in groente en fruit in diverse
stadia van de huishondelijke bereiding (april 1974)
TVL. (1975) Tasman Vaccine Laboratory Limited. Letter dealing with
bromophos-ethyl residues in sheep; 22 September 1975 (Unpublished)
Wollongbar Agricultural Research Station (N.S.W.), Dep. of
Agriculture. (1969) (Unpublished data on bromophos-ethyl residues in
butter of cows [after Nexagan(R)-dipping], 31.3.69)
See Also:
Toxicological Abbreviations
Bromophos-ethyl (WHO Pesticide Residues Series 2)
Bromophos-ethyl (Pesticide residues in food: 1977 evaluations)