Trichloroethyl phosphate

229.383

229.38

206-185-6

J712EO9048

DTXSID9023700

WHITE OR ALMOST WHITE POWDER

N - Nervous system

2919900090

66.8

1.46590

1.891 g/cm3

321.2ºC at 760 mmHg

148.1ºC

1.53

1 g in 250 ml alcohol; almost insol in ether

LD50 orl-rat: 850 mg/kg GISAAA 33(11),101,68

SALINE

STABLE IN LIGHT, UNSTABLE IN HEAT ABOVE ROOM TEMP /MONOSODIUM/

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

BLALOCK CC; DRUG EVALUATION DATA: TRICLOFOS SODIUM; DRUG INTEL CLIN PHARM 7 (MAR): 126-8 (1973). MONOGRAPH ON TRICLOFOS SODIUM INCLUDING CHEMISTRY, MECHANISM OF ACTION, TOXICOLOGY, BIOPHARMACEUTICS, MFR CLAIMS, SIDE EFFECTS & ADVERSE REACTIONS, DRUG INTERACTIONS, DOSAGE & ADMIN & COST IS PRESENTED.

...TRICLOFOS.../IS/ SLOWLY HYDROLYZED IN STOMACH TO YIELD CHLORAL HYDRATE AND .../IT HAS/ BEEN SHOWN TO DECR WARFARIN HALF-LIFE BY INCR AMT OF UNBOUND WARFARIN AVAILABLE FOR METABOLISM.|...TRICLOFOS /IS/...METABOLIZED TO YIELD TRICHLOROETHANOL /WHICH/ WILL INTERACT WITH ALCOHOL.|It is proposed that a metabolite of triclofos (trichloroacetic acid) displaces warfarin from plasma protein binding.

Triclofos's production and use as a medicinal drug may result in its release to the environment through various waste streams(1).

TERRESTRIAL FATE: An estimated Koc of 352(1,2,SRC) indicates that triclofos will have moderate mobility in soil(3). Under alkaline soil conditions, hydrolysis of triclofos may be rapid and will be expected to be a major fate process for this compound; the rate of hydrolysis in neutral or slightly acid soil environments should be slower(4). Triclofos is not expected to volatilize from soil surfaces based on an estimated Henry's Law constant of 1.41X10-13 atm-cu m/mole(5).|AQUATIC FATE: Hydrolysis of triclofos, particularly in alkaline waters, will be a major fate process for this compound; in neutral or slightly acidic water, triclofos will hydrolyze less rapidly(1). Triclofos is not expected to volatilize from water surfaces based on an estimated Henry's Law constant of 1.41X10-13 atm-cu/mole(2). If released to an aquatic environment, triclofos is not expected to bioconcentrate with an estimated BCF value of 25(3,4,SRC).|ATMOSPHERIC FATE: Based on an estimated vapor pressure of 2.13X10-6 mm Hg at 25 °C(1,SRC), triclofos can exist in both the vapor phase and particulate phase in the ambient atmosphere(2,SRC). It will degrade fairly rapidly in the vapor phase by reaction with photochemically produced hydroxyl radicals with an estimated half-life of 10 days(3,SRC). Particulate phase triclofos may be removed physically from air by wet and dry deposition(SRC).

The rate constant for the vapor phase reaction of triclofos with photochemically produced hydroxyl radicals has been estimated as 1.58X10-12 cu-cm/molecule-sec at 25 °C(1). This corresponds to an atmospheric half-life of about 10 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1,SRC). Hydrolysis of triclofos is expected to be rapid. Hydrolysis of phosphate esters is generally promoted by alkaline conditions as the phosphate ester undergoes second order nucleophilic reactions involving cleavage of the O-P bond due to hydroxide ions(2). A half-life of 852 years has been reported for methyl phosphate in water at 25 °C and at a pH 4.17(3); the reaction rate was 2.57X10-11 1/sec(3). The three chlorines on the ethyl will act as electron withdrawing groups and will promote hydrolysis by OH-(2). In addition, monoalkyl phosphates, which exist as mono and dianions at common environmental pH's, are generally more susceptible to hydrolysis than the di- or triesters. Thus under alkaline conditions triclofos may hydrolyze fairly rapidly(2,SRC).

Based on an estimated log Kow of 1.13(1), the BCF of triclofos is estimated as 4.2 from a regression-derived equation(2,SRC). This BCF value indicates that bioconcentration is not an important fate process for triclofos(SRC).

Using a regression-derived equation(1) and an estimated log Kow of 1.13(2), the Koc for triclofos was estimated as 98(SRC). According to a suggested classification scheme, this Koc value suggests that triclofos will have moderate mobility in soil(3). As triclofos should be fairly water soluble, leaching of this compound may occur under certain environmental conditions(SRC).

The Henry's Law constant for triclofos is estimated as 1.41X10-13 atm-cu m/mole(1,SRC). This value indicates that triclofos is essentially non-volatile from water surfaces(2).

Hypnotics and Sedatives|A HYPNOTIC AGENT SUGGESTED FOR INSOMNIA CHARACTERIZED BY DIFFICULTY IN FALLING ASLEEP, NOCTURNAL AWAKENING, & EARLY MORNING AWAKENING. /TRICLOFOS SODIUM/|A DOSE OF TRICLOFOS SODIUM OF 1.5 G WILL YIELD BLOOD LEVEL OF TRICHLOROETHANOL APPROX EQUAL TO THAT FROM 900 MG OF CHLORAL HYDRATE. /TRICLOFOS SODIUM/|In a study involving seven healthy subjects stabilized on warfarin, triclofos considerably incr the hypoprothrombinemic response initially, with a gradual diminution of this effect after the first week....patients receiving chronic oral anticoagulant therapy who are started on triclofos are only at risk of hemorrhage during the first two weeks of combined therapy.

IT IS CONTRAINDICATED IN PT WITH MARKED RENAL OR HEPATIC IMPAIRMENT. TRICLOFOS SODIUM MAY BE HABIT FORMING AND IS SUBJECT TO SAME WARNINGS, PRECAUTIONS, AND DRUG INTERACTIONS AS CHLORAL HYDRATE... EXCEPT FOR SINGLE DOSE TO INDUCE SLEEP DURING ECG, DRUG CANNOT BE RECOMMENDED IN CHILDREN UNDER 12 YR OF AGE. /TRICLOFOS SODIUM/|In patients on chronic oral anticoagulant therapy who require sedative-hypnotics...use drugs which...do not interact such as flurazepam (dalmane) or diazepam (valium). If triclofos is used, the patient should be monitored closely during the first two weeks of triclofos therapy.

HYDROLYSIS KINETICS WAS STUDIED AT PH 0-7.8, TEMP 80.1-98.4 °F & IONIC STRENGTH 0.02-1.50. VARIOUS MECHANISTIC POSSIBILITIES FOR THE DIFFERENT NATURES OF TRICLOFOS SODIUM AT THE VARYING RANGES OF PH, TEMPERATURE AND IONIC STRENGTH ARE DISCUSSED. /TRICLOFOS SODIUM MONOPHOSPHATE ESTER/|After 6 hr, 4.6% of 15 mg/kg and 22 mg/kg dose of triclofos sodium given orally to seven healthy people, was recovered in the urine.

...IS RAPIDLY DEPHOSPHORYLATED, PRINCIPALLY IN GUT, TO TRICHLOROETHANOL... TRICLOFOS SODIUM PRODUCES A PEAK TRICHLOROETHANOL LEVEL IN 1 HR... /TRICLOFOS SODIUM/|METABOLISM OF CHLORAL HYDRATE AND TRICLOFOS SODIUM WAS COMPARED IN SEVEN HEALTHY PEOPLE WHO INGESTED 15 MG/KG & 22.5 MG/KG. TRICHLOROETHANOL WAS PRODUCED. AFTER 6 HR 4.6% OF TRICLOFOS SODIUM WAS RECOVERED IN URINE AS TRICHLOROETHANOL & TRICHLOROACETIC ACID.

...IT HAS A HALF-LIFE OF APPROXIMATELY 8 HR. /TRICLOFOS SODIUM/

PRETERM INFANT WITH ACCIDENTAL TRICLOFOS SODIUM POISONING DEVELOPED DEEP COMA, SEVERE HYPOTHERMIA, HYPOTENSION & LACK OF PRIMITIVE & DEEP TENDON REFLEXES.|THIRTY PT COMPLAINING OF INSOMNIA WERE STUDIED IN DOUBLE-BLIND TRIAL WITH CROSSOVER OF FINORGAL, NITRAZEPAM & TRICLOFOS SODIUM. FINORGAL PRODUCED SIMILAR RESULTS TO TRICLOFOS SODIUM. SIDE-EFFECTS WERE NOT SERIOUS. NO DRUG TOXICITY DEVELOPED OVER THREE WK PERIOD OF TREATMENT.

2,2,2-trichloroethyl dihydrogen phosphate, sodium salt

Syrup: 500 mg/5 ml|Tablets: 750 mg; liquid: 100 mg/ml

Ethanol, 2,2,2-trichloro-, dihydrogen phosphate: ACTIVE

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients