Prothiofos is a colorless liquid. It is nearly insoluble in water (1.7 mg/L
at 20 C) but readily soluble in most organic solvents. Log
Kow = 5.67. It is relatively stable in aqueous media; DT50
values (22 C) at pH 4, 7, and 9 are 120, 280, and 12 d, respectively.
Prothiofos is used to control chewing insects in a range of crops
including vegetables, fruit, maize, sugar cane and ornamentals.
ChEBI: An organic thiophosphate that is the 2,4-dichlorophenyl ester of O-ethyl S-propyl dithiophosphoric acid.
The commercial production of prothiofos involves a multi-step chemical synthesis beginning with the chlorination of phenol to produce 2,4-dichlorophenol. This intermediate is then reacted with phosphorus pentasulfide or thiophosphoryl chloride and ethanol to form O,O-diethyl phosphorothioic chloride, a key activated precursor. In the final step, esterification occurs between the phosphorus intermediate and 2,4-dichlorophenol in the presence of a base such as pyridine, yielding prothiofos.
Non-systemic with contact and stomach action, Acetylcholinesterase (AchE) inhibitor.
A report by Nihon Tokushu Noyaku Seizo K.K. (1979) (now Nhon Bayer
Agrochem K.K.) has summarised the nature of the photolysis products
and metabolites formed by prothiofos in plants, insects, chicken, mice,
rats, guinea-pigs and rabbits. Major routes for the metabolism of prothiofos
include activation via oxidative desulfuration to the oxon and detoxification
by dearylation to give 2,4-dichlorophenol which occur in all
media. In addition, cleavage of the P-S bond and loss of the propanethiol
moiety is an important detoxification mechanism in mammals but not
insects and dechlorination by reductive loss of the 2-chlorine substituent
in the phenyl ring occurs in soil, plants and photochemically. Stage II
metabolism results in the formation of the glucoside of 2,4-dichlorophenol
in plants and insects and the glucuronide and sulfate ester in mammals.
The principal metabolic routes are
activation by oxidative desulfuraton and detoxification by
dearylation and cleavage of the PS bond in both animals
and plants. Prothiofos is strongly adsorbed in soil; the
half-life under field conditions is 1–2 months.
Prothiofos is hydrolysed at pH 4,7 and 9 with DT50 values of 120,280 and
12 days, respectively (PM). Takase et al. (1982) examined the photolysis
of hexane, methanol, aqueous methanol solutions and thin films of [2H-ethyl]
prothiofos and unlabelled prothiofos. The compound was irradiated
by UV light from a high pressure mercury vapour lamp (λmax 360 nm)
for up to 4 hours or by sunlight for 15 days. Photolysis products were
purified by TLC and identified by GC-MS. Under UV irradiation, prothiofos
was degraded with a half-life of from 60 minutes (hexane solution)
to 420 minutes (thin film). Prothiofos was photolysed under UV light by
five main mechanisms: (a) reductive dechlorination at the 2-position of
the phenyl ring, (b) desulfuration to the oxon ( P=O ) products, (c) cleavage
of the P-S bond and loss of propanethiol, (d) cleavage of the P-O-aryl
linkage resulting in the production of phenols and (e) dechlorination at
the 4-position of the phenyl ring. The main photochemical reaction product
was formed by reductive dechlorination of the 2-position of the
phenyl ring to give 4-chloroprothiofos (2). The next most important
mechanism was photooxidation of the P=S moiety (a common reaction of
phosphorothioates and also noted with parathion, fenitrothion, disulfoton
and fenthoate) to give prothiofos oxon (3), which was subsequently 2-
dechlorinated to give 4. Loss of propanethiol via cleavage of the P-S bond
of prothiofos oxon (3) and the 2-dechlorinated oxon (4) afforded 5 and 6,
respectively, in aqueous solution. In hexane solution photoproducts 7
and 8 were formed by the substitution of the Pr-S group by a chlorine
atom from the ring.
Dearylation by cleavage of the P-O-aryl linkage gave rise to 2,4-
dichlorophenol(9) and 4-chlorophenol(10) which were formed in greater
yields in the aqueous media.4-Dechlorination was a minor route, with only a trace of the di-dechloroprothiofos photoproduct (11) being
detected. In hexane solution only, a number of other photoproducts were
formed of which the most interesting (12) was formed via the displacement
of the 2-chlorine atom by the P-S sulfur (Scheme 1).
Under natural sunlight conditions in hexane the level of photodegradation
was considerably less. The major photoproducts were prothiofos
oxon (3), 4-chloroprothiofos (2) and its oxon (4) and the cyclic
phosphorodithioate (12).
The acute oral LD50
for rats is 1390–1569 mg/kg. Inhalation LC50 (4 h) for
rats is >2.7mg/L air. NOEL (2 yr) for rats is 5mg/kg
diet (0.25 mg/kg/d). ADI is 0.1 μg/kg b.w. Prothiofos
administered to rats is rapidlymetabolized, and 98% of the
dose is excreted in 72 h.
