FENTHION JMPR 1975
Explanation
Fenthion was last evaluated by the 1971 FAO/WHO Joint Meeting
(FAO/WHO, 1972). Concerning residues in food and their evaluation,
only information on the frequency and level of fenthion residues in
food commodities in commerce were listed as desirable. No such data
have become available.
New information on the toxicology, composition of technical
fenthion and on national tolerances and pre-harvest intervals has been
supplied and is listed in the following monograph addendum.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOCHEMICAL ASPECTS
Effects on enzymes and other biochemical parameters
When fenthion was administered at doses of 0.5 mg/kg orally to
rats, and 1-8 mg/kg intravenously to cats, significant inhibition of
and effects on heart rate and blood pressure were observed. However,
an intravenous dose of 0.3 mg/kg to cats produced no significant
changes in blood pressure, heart rate or other physiological
parameters (Wills et al., 1975).
TOXICOLOGICAL STUDIES
Special studies on reproduction
Mouse
In a five generation reproduction study (2 litters per
generation) two groups of Charles River CD 1 mice consisting of 14
females, 10 males; and 22 females, 10 males, received 0 and 60 ppm
fenthion respectively in their drinking water. In the parameters
studied (reproductive performance, lactation, viability and growth
rate of pups) the principal effect was a significant increase in pup
mortality especially in the 2nd, 3rd and 4th generations. The highest
mortality appeared to be in the first postnatal week. No
histopathological changes were noted in the liver or kidney. There was
no evidence of teratogenic potentials (Budreau and Singh, 1973b).
Special studies on teratogenicity
Mouse
Pregnant Charles River CD 1 mice were injected intraperitoneally
with single doses of 40, 80 and 160 mg/kg body weight at various time
periods during organ ogenesis. Foetuses were removed by caesarean
section on days 16 and 18 and viscera and skeletal structure examined
for abnormalities. The frequency of resorptions and festal deaths was
not affected. Foetal weights were reduced significantly. Although the
number and type of abnormalities were increased when compared to the
control group, this did not appear to be dose-related. There was no
apparent teratogenic effect, however, the incidence of resorptions was
increased when fenthion was injected intraperitoneally for three
consecutive days (day 9, 10, 11 of gestation) at 20 mg/kg (Budreau and
Singh, 1973a).
Fenthion was administered orally to groups of female rats for one
generation (two litters) at dosage levels of 5 mg/kg body weight and
10 mg/kg body weight from both day 1 through day 7 and day 8 through
day 10 of gestation. Animals were sacrificed on day 21, foetuses were
removed by caesarean section and examined for internal and external
abnormalities. No malformations were observed. The incidence of
resorptions was increased and weight of foetuses reduced. The second
progeny from these females were not affected. In a further study rats
were given fenthion at a dosage level of 5 mg/kg body weight from day
1 through day 13 of gestation, There was no evidence of teratogenesis.
However, the incidences of foetal resorption and abortion were
increased. During the lactation period there was an increased
mortality and a decrease in the body weight gain of the pups. By day
45 postpartum surviving new born had recovered normal weight
(Fytizas-Danielidou, 1971).
Acute toxicity
Mouse (F) I.P. 200-240 mg/kg Budreau and Singh 1973
Observations in man
The potential dermal and respiratory exposure to fenthion during
field application by hand gun power spray equipment, back-pack hand
pressure sprayer and hand granular dispersal for mosquito control was
studied over two work seasons (Fytizas-Danielidou, 1971). Human
workers exposed to 3.6-12.3 mg/h (dermal) or <0.02-0.09 mg/h
(inhalation), equivalent to 0.5-1.5 mg/kg/day (dermal) and 0.01-0.05
mg/kg/day (inhalation), showed a decrease in plasma, but not
erythrocyte, cholinesterase activity (Wolfe et al., 1974).
Comment
Although additional data have been made available relating to
reproduction, teratology and potential human exposure to fenthion,
adequate two-year feeding studies and data to elucidate the mechanism
of action of prolonged cholinesterase inhibition as required by the
1971 Joint Meeting, have not been provided. Sufficient data was
available to extend the existing temporary acceptable daily intake.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect:
Rat: 3 ppm in the list equivalent to 0.15 mg/kg bw
Dog: 2 ppm in the diet equivalent to 0.05 mg/kg bw
Estimate of temporary acceptable daily intake for man
0 - 0.0005 mg/kg bw
TABLE 1. Composition of technical fenthion (Bayer AG, 1975)
O,O-dimethyl O-(3-methyl-4-methylthiophenyl)
phosphorothioate min. 96%
O,S-dimethyl O-(3-methyl-4-methylthiophenyl)
phosphorothioate max. 1.0%
O-methyl O-(3-methyl-4-methylthiophenyl)
phosphorothioate max. 0.5%
3-methyl-4-methylthiophenylphenol max. 0.5%
bis-O,O-diethylphosphorothioic anhydride max. 0.5%
O,O-dimethyl O-(3-methyl-4,6-di(methylthio)phenyl
phosphorothioate max. 1.5%
1-methylthio-2-methyl-4-methoxybenzene max. 0.5%
O,O,O-trimethyl phosphorothioate max. 0.1%
water max. 0.1%
TABLE 2. National tolerances for fenthion reported to the Meeting
(changes and additions since the 1971 evaluation)
Tolerance Pre-harvest
Country Commodity (mg/kg) interval (days)
Australia General 14
Milk and milk products
(fat basis) 0.2
Cereals, fruit, 2.0
vegetables
Meat of cattle 1.0 1
Brazil Fruit 1.0 14
All other crops 10
Federal Republic Cherries 14
of Germany
Pome fruit 21
Fruit generally 1.0
Hungary General 1.0 21
Israel Apples, apricots,
peaches 2.0
cucurbits, olives
olive-oil, onions,
pears 1.0
Japan Rice 0.05 14 - 30
Potatoes 0.05 7
Poland Apples, plums 28
TABLE 2. (continued)
Tolerance Pre-harvest
Country Commodity (mg/kg) interval (days)
South Africa General 2.0
Apples, apricots,
coffee, cucurbits,
guavas, peaches, pears, 10
plums, pome fruit
Spain Cereals, citrus fruit,
fruit, olives, rice 30
USA Rice 0.1 30
Rice straw 0.5
Yugoslavia General 0.5
Fruit, olives 21
APPRAISAL
New information has been provided concerning the composition of
technical grade fenthion. The minimum content of O,O-dimethyl
O-(3-methyl-4-methylthiophenyl) phosphorothioate is 96% as already
reported (FAO/WHO, 1972) but in recent production the impurity
O,O-dimethyl O-(3-methyl-4,6-di(methylthio)phenyl) phosphorothioate
has decreased from 5-7% to 1.5%. New national tolerances have been
established for several commodities for which no residue data or only
limited data were available to the 1971 Meeting. The appropriate
residue data should therefore be supplied to the Joint Meeting.
Limited residue data on fruit and vegetables moving in commerce
have been received. With one exception (0.5 mg/kg apples) residues in
142 samples (including 125 samples of apples) were below 0.02 mg/kg in
apples, cabbage, cherries, cucumbers, kohlrabi, lettuce, peaches and
pears. The samples were from food inspections in Hungary (1974) and
the Netherlands (1975).
FURTHER WORK OR INFORMATION
REQUIRED (by 30 June 1978, in addition to the information listed in
FAO/WHO 1972a, p.43 and before additional maximum residue limits can
be recommended)
1. Residue data from supervised trials in accordance with good
agricultural practice on other citrus fruit (especially
lemons), coffee, cucurbits, onions and potatoes, and
additional residue data on sugar beet roots and tops.
DESIRABLE
See FAO/WHO 1972a, p.43
REFERENCES
Bayer AG. (1975) Pflanzenschutz-Anwendungstechnik, Leverkusen, 1975
(Unpublished)
Budreau, C.H. and Singh, R.P. (1973a) Teratogenicity and
Embryotoxicity of Demeton and Fenthion in CF 1 Mouse Embryos. Tox.
Appl. Pharm., 24, 325-332.
Budreau, C.H. and Singh, R.P. (1973b) Effect of Fenthion and
Dimethoate on Reproduction in the Mouse. Tox. Appl. Pharm., 26,
29-38.
Fytizas-Danielidou, R. (1971) Effects des pesticides sur la
reproduction des rats blancs. I. Lebaycide. Fakulteit van de
Landbouwwetenschappen. 23. Internationaal Symposium over Fytofarmacie,
4 Mei, 1971.
Wills, J.H., Groblewski, G.E. and Coulston, F. (1975) Status report to
Bayer AG. West Germany from Institute of Comparative and Human
Toxicology, Albany Medical College, Albany, New York submitted to WHO
by Bayer AG.
Wolfe, H.R., Armstrong, J.F. and Durham, W.F. (1974) Exposure of
Mosquito Control Workers to Fenthion. Mosquito News, 34, 263-267.
See Also:
Toxicological Abbreviations
Fenthion (ICSC)
Fenthion (WHO Pesticide Residues Series 1)
Fenthion (Pesticide residues in food: 1977 evaluations)
Fenthion (Pesticide residues in food: 1978 evaluations)
Fenthion (Pesticide residues in food: 1979 evaluations)
Fenthion (Pesticide residues in food: 1980 evaluations)
Fenthion (Pesticide residues in food: 1983 evaluations)
Fenthion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
Fenthion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
Fenthion (Pesticide residues in food: 1997 evaluations Part II Toxicological & Environmental)