TDCPP is a halogenated phosphate triester flame retardant. Its mechanism of toxicity involves the induction of oxidative stress in cells. Evidence for this includes the attenuation of its toxic effects by the antioxidant N-acetylcysteine. It causes cytostasis at lower concentrations and cell toxicity at higher concentrations in human kidney cells [2].

Cell viability remains unaffected by TDCPP exposure at concentrations higher than 68 μg/mL. When exposed to 136 μg/mL TDCPP, HCEC displayed a 16% reduction in cell viability. Furthermore, TDCPP caused all viable cells to be completely reduced (87%) up until treatment to ≥272 μg/mL of TDCPP. TDCPP's LC50 value was determined by indirect regression analysis based on cell viability, and it was 202 μg/mL. Cell wetness increased in TDCPP-exposed cells at concentrations higher than in control cells. In comparison to controls, antioxidant Bcl-2 protein expression increased up to 1.4 times at 2 μg/mL TDCPP and 1.2 times at 20 μg/mL. times, but at 200 μg/mL, it dynamically dropped to 0.4 times. The quantity of caspase-3 activity introduced was 2.1 times greater than the control at 200 μg/mL TDCPP [1]. TDCPP affects cell viability and toxicity at similar values (IC50 = 171 μM and 168 μM, respectively), although it inhibits cell growth at lower concentrations (IC50 = 27 μM) [2].

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In HK-2 human kidney proximal tubule cells, TDCPP inhibited cell growth at lower concentrations. The IC50 for cell growth inhibition (cytostasis) was 27 µM (95% confidence interval: 20-36 µM) after up to 96 hours of exposure [2].
TDCPP affected cell viability and cell toxicity at higher concentrations. The IC50 for cell viability was 168 µM (95% CI: 160-177 µM), and the IC50 for cell toxicity (measured by a tetrazolium reduction assay) was 171 µM (95% CI: 162-181 µM) after 24 hours of exposure [2].
Protein synthesis was not significantly inhibited by TDCPP until concentrations exceeded 250 µM, suggesting that inhibition of protein synthesis is not a major factor in TDCPP-induced cytostasis [2].
Cell cycle analysis showed that at 100 µM TDCPP, there was a significant increase in the G1 phase cell population and a complementary significant decrease in G2/M phase cells, suggesting a partial G1 arrest. At concentrations of 150-250 µM, a sub-G1 cell population was evident, suggestive of apoptotic cells [2].
The antioxidant N-acetylcysteine attenuated TDCPP-induced cell toxicity in a dose-dependent manner when administered after TDCPP exposure. Pre-treatment with NAC before TDCPP exposure had no protective effect [2].

HK-2 cells were cultured in DMEM with 10% FBS and antibiotics at 37°C. For TDCPP treatment, stock TDCPP was diluted in DMSO, filter-sterilized, and added to media at a constant DMSO concentration of 0.1% v/v. Control cells received equivalent DMSO vehicle [2].
Cell growth was measured by counting cells with a Z2 Coulter Counter at 24-hour intervals over 96 hours of continuous exposure to increasing concentrations of TDCPP. The slopes of the growth curves were compared to determine the IC50 for cytostasis [2].
Cell viability was assessed using the trypan blue dye exclusion method. Adherent cells were released, incubated with 0.2% trypan blue for 5 minutes, and scored on a hemocytometer [2].
Cell toxicity was measured using the CellTiter-Blue cell viability assay according to the manufacturer's instructions. Fluorescence was monitored at excitation 560 nm and emission 590 nm [2].
Total protein levels were measured using the Pierce BCA Protein Assay Kit. Cell pellets were lysed in CellLytic M and analyzed following the microplate version of the assay procedure, with absorbance monitored at 562 nm [2].
Cell cycle analysis was performed on randomly cycling cell populations. Cells were fixed in ice-cold 100% ethanol, stained with a propidium iodide solution (50 µg/mL propidium iodide, 0.1 mg/mL sodium citrate, 2 µg/mL ribonuclease A, and 0.03% Triton X-100) for 5 minutes, and analyzed using an LSR-Fortessa flow cytometer. Data were analyzed with FlowJo software [2].
For antioxidant studies, cells were treated with 1-10 mM N-acetylcysteine for 1, 3, or 24 hours either before or after exposure to increasing concentrations of TDCPP [2].

[1]. Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health. Environ Pollut. 2017 Nov;230:22-30.

[2]. Flame retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP) toxicity is attenuated by N-acetylcysteine in human kidney cells. Toxicol Rep. 2017 May 17;4:260-264.

According to an independent committee of scientific and health experts, tris(1,3-dichloro-2-propyl) phosphate (TDCPP) may be carcinogenic. Tris(1,3-dichloroprop-2-yl) phosphate is a trialkyl phosphate ester. See also: Tris(2,3-dichloroprop-2-yl) phosphate (note moved here).

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TDCPP is a high-volume additive flame retardant used in polyurethane foams, resins, plastics, textile coatings, and rubber. It can comprise up to 5% of the total weight in foam products. Environmental studies have found TDCPP in dust from 96% of US households at levels >2 ppm, with some as high as >50 ppm. Biomonitoring studies have detected TDCPP in human breast milk, adipose tissue, semen, and urine [2].
While regulatory agencies like the EPA and IARC generally consider TDCPP to have low toxicity, California's Proposition 65 lists it as a potential carcinogen. Animal studies have shown that TDCPP can disrupt development, reproduction, and endocrine functions, and increase the risk for some cancers [2].
This study is the first report of TDCPP toxicity in HK-2 cells, a human kidney proximal tubule cell line. The results show that low micromolar concentrations of TDCPP cause cytostasis, while higher concentrations induce cell toxicity, which can be partially reversed by the antioxidant NAC. This suggests that oxidative stress plays a role in TDCPP toxicity [2].
The attenuation of TDCPP toxicity by NAC, particularly when administered after TDCPP exposure, suggests that antioxidants may be effective countermeasures for some organohalogen exposures [2].

C9H15CL6O4P

430.9048

427.883

13674-87-8

26177

Colorless to light yellow liquid

1.5±0.1 g/cm3

457.4±40.0 °C at 760 mmHg

-64°C

377.7±35.0 °C

0.0±1.1 mmHg at 25°C

1.497

1.79

0

4

12

20

243

0

ASLWPAWFJZFCKF-UHFFFAOYSA-N

InChI=1S/C9H15Cl6O4P/c10-1-7(2-11)17-20(16,18-8(3-12)4-13)19-9(5-14)6-15/h7-9H,1-6H2

tris(1,3-dichloropropan-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)

Ethanol : ~100 mg/mL (~232.07 mM)
DMSO : ≥ 62.5 mg/mL (~145.05 mM)

Solubility in Formulation 1: 33.33 mg/mL (77.35 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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: ≥ 2.08 mg/mL (4.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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 3: ≥ 2.08 mg/mL (4.83 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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 4: ≥ 2.08 mg/mL (4.83 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 20.8 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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Solubility in Formulation 5: 33.33 mg/mL (77.35 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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