Absorption, Distribution and Excretion
radiolabeled dosing solution was prepared by mixing radiolabeled tris(1-chloro-2-propyl) phosphate with unlabeled Fyrol PCF in a solvent of ethanol, emulsifier, and water. The dosing solution was prepared and analyzed by administering approximately 0.5 mL (2 mL/kg body weight) of the solution to rats each time, containing 20 or 200 mg/kg body weight of tris(1-chloro-2-propyl) phosphate and 40 μCi of radiolabeled tris(1-chloro-2-propyl) phosphate. The study was divided into two phases. During the recovery phase, animals were administered the drug, and urine, feces, and exhaled breath were collected at 11 time points over 8 days. Five male and five female animals received an oral dose of 200 mg/kg, and five other male animals received a single oral or intravenous dose of 20 mg/kg. During the plasma phase, animals were administered the drug, and blood, urine, and fecal samples were collected at 18 predetermined time intervals over 8 days. In both phases, at least five animals of each sex were orally administered a dose of 200 mg/kg, while five male animals received a single oral or intravenous dose of 20 mg/kg. Urine, feces, exhaled breath, tissue, and serial blood samples were collected and total radioactivity was analyzed… In both male and female rats, tris(1-chloro-2-propyl) phosphate and its metabolites were rapidly eliminated following a single bolus injection. …No differences were observed between sexes or doses. Biphasic (plasma) elimination followed first-order kinetics. While urinary excretion was identified as the primary route of elimination, the extent of elimination depended on both the administered dose and route of administration. The same was true for fecal elimination. Elimination in urine and feces was sex-independent, with 89% of the dose eliminated within 72 hours. Eight days later, the total body load was less than 1%... Radiolabeled (14)C-tris(1-chloro-2-propyl)phosphate (GC purity 99%) was dissolved in olive oil at a dose of 16.4 mg/kg body weight (0.05 mmol/kg) and administered orally to 3–5 male Wistar rats. The absorption rate was calculated by measuring the cumulative urinary and exhaled air radioisotope content 7 days after administration, and the radioisotope content in the blood and tissues of rats sacrificed at 3, 6, 12 hours and 1, 3, or 7 days after administration. Radiolabeled TMCPP was rapidly absorbed. Radiolabeling was detectable throughout the body 3 hours after administration. After 7 days, 76% of the oral dose had been excreted in urine and exhaled air or remained in the cadaver. Another 22% was excreted in feces. However, TMCPP undergoes enterohepatic circulation, so it is unclear whether this portion includes unabsorbed TMCPP, TMCPP excreted in bile, or both. Therefore, at least 76% of TMCPP was absorbed after oral administration to rats. (14)C-labeled TMCPP was dissolved in olive oil and administered orally to male Wistar rats at a dose of 50 μmol/kg body weight. Three hours later, the highest (14)C concentrations were found in the liver (29 nmol/g tissue) and kidneys (27 nmol/g tissue), followed by the lungs (9 nmol/g tissue). Concentrations in blood, heart, spleen, brain, testes, adipose tissue, and muscle were all below 4 nmol/g tissue. Wistar rats were orally administered 50 μmol/kg body weight of TMCPP. Most of the 14C-labeled TMCPP was excreted within 24 hours, with less than 1% remaining in tissues after 7 days. 67% was excreted in urine, 22% in feces, and 8% in exhaled gases. Furthermore, bile excretion was measured in cannulated rats 48 hours after administration of the same oral dose. Bile radioactivity peaks within 2 hours after administration, and after 48 hours, bile excretion accounts for approximately 45% of the administered dose.

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Metabolism / Metabolites
radiolabeled dosing solution was prepared by mixing radiolabeled tris(1-chloro-2-propyl) phosphate with unlabeled Fyrol PCF in a solvent of ethanol, emulsifier, and water. The dosing solution was prepared and analyzed by administering approximately 0.5 mL (2 mL/kg body weight) of the solution to rats each time, containing 20 or 200 mg/kg body weight of tris(1-chloro-2-propyl) phosphate and 40 μCi of radiolabeled tris(1-chloro-2-propyl) phosphate. The study was divided into two phases. During the recovery phase, animals were administered the drug, and urine, feces, and exhaled breath were collected at 11 time points over 8 days. Five male and five female animals received an oral dose of 200 mg/kg, and five other male animals received a single oral or intravenous dose of 20 mg/kg. During the plasma phase, animals were administered the drug, and blood, urine, and fecal samples were collected at 18 predetermined time intervals over 8 days. In two phases, at least five animals of each sex were orally administered a dose of 200 mg/kg, while five male animals were given a single oral or intravenous dose of 20 mg/kg. Urine, feces, exhaled breath, tissue, and serial blood samples were collected and analyzed for total radioactivity. Metabolites of tris(1-chloro-2-propyl)phosphate were isolated, quantified, and identified from rat urine and feces… At both dose levels, identifiable metabolites accounted for 75–78.5% of the radiocarbon in urine and feces of both sexes. O,O-[bis(1-chloro-2-propyl)]-O-(2-propionic acid)phosphate was identified as the major metabolite, exceeding 50% of the dose in urine and feces of both sexes at both dose levels.

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Biological Half-Life
The terminal (plasma) half-life was 48.7 ± 6.0 hours. Following a single oral administration of (14)C-labeled TMCPP to rats, the biological half-lives in the blood were 12 hours (phase I) and 59 hours (phase II), respectively. Between 1997 and 2006, the levels of tris(1-chloro-2-propyl)phosphate in mixed breast milk collected from Swedish women after their first childbirth ranged from 22 to 82 ng/g lipids.

Non-Human Toxicity Values
LD50 rat (male) oral administration 4200 mg/kg body weight
LD50 rat (female) oral administration 2800 mg/kg body weight
LD50 rat (male) oral administration 2710 mg/kg body weight
LD50 rat (male) oral administration 2000 mg/kg body weight
For more complete non-human toxicity data for tris(2-chloroisopropyl) phosphate (of 28), please visit the HSDB record page.

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Toxicity Data
LC50 (rat) > 4,600 mg/m3/4 hours

[1]. Comparative studies on absorption, distribution, and excretion of flame retardants halogenated alkyl phosphate in rats. Eisei kagaku, 1988, 34(2): 102-114.

Tris(2-chloroisopropyl) phosphate is a clear, colorless, viscous liquid. (NTP, 1992)
Tris(1-chloropropyl-2-yl) phosphate is a trialkyl phosphate ester.

C9H18CL3O4P

327.57

326.001

13674-84-5

26176

Colorless to light yellow liquid

1.3±0.1 g/cm3

358.5±22.0 °C at 760 mmHg

-42 °C

249.7±30.0 °C

0.0±0.8 mmHg at 25°C

1.462

1.53

0

4

9

17

216

0

ClC([H])([H])C([H])(C([H])([H])[H])OP(=O)(OC([H])(C([H])([H])[H])C([H])([H])Cl)OC([H])(C([H])([H])[H])C([H])([H])Cl

KVMPUXDNESXNOH-UHFFFAOYSA-N

InChI=1S/C9H18Cl3O4P/c1-7(4-10)14-17(13,15-8(2)5-11)16-9(3)6-12/h7-9H,4-6H2,1-3H3

tris(1-chloropropan-2-yl) phosphate

Tris(1-chloropropan-2-yl) phosphate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~200 mg/mL (~610.6 mM; with ultrasonication)

Solubility in Formulation 1: ≥ 5 mg/mL (15.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 5 mg/mL (15.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 5 mg/mL (15.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (50.0 mg/mL) to 900 μL of corn oil and mix well.

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 (Please use freshly prepared in vivo formulations for optimal results.)