Prothiofos

Description

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.

The Uses of Prothiofos

Prothiofos is used to control chewing insects in a range of crops including vegetables, fruit, maize, sugar cane and ornamentals.

Definition

ChEBI: An organic thiophosphate that is the 2,4-dichlorophenyl ester of O-ethyl S-propyl dithiophosphoric acid.

Metabolic pathway

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.

Metabolism

The principal metabolic routes are activation by oxidative desulfuraton and detoxification by dearylation and cleavage of the P?S bond in both animals and plants. Prothiofos is strongly adsorbed in soil; the half-life under field conditions is 1–2 months.

Toxicity evaluation

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.

Degradation

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 (λ_max 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).