Absorption, Distribution and Excretion
Following intravenous or oral administration, it is primarily excreted in the urine and bile. It appears to be rapidly cleared from the blood, with most being cleared within 5–7 hours after dialysis. In a study of subjects receiving hemodialysis, blood transfusions, or who had been exposed to PVC medical products, di(2-ethylhexyl) phthalate levels (μg/g wet tissue) in the following tissues were observed: brain (1.9), heart (0.5), kidneys (1.2–2.2), liver (1.5–4.6), lungs (1.4–2.2), and spleen (2.2–4.7). Di(2-ethylhexyl) phthalate levels have been reported in the heart tissue of newborns who underwent umbilical catheterization (whether alone or with concurrent blood product transfusions) compared to untreated newborns. (Infants) For more complete data on the absorption, distribution, and excretion of di(2-ethylhexyl) phthalates (67 in total), please visit the HSDB record page. Metabolites/Metabolites It is hypothesized that the teratogenic di(2-ethylhexyl) phthalate (DEHP) works by hydrolysis in vivo to 2-ethylhexanol (2-EXHO), which is further metabolized to 2-ethylhexanoic acid (2-EXHA), a proximal teratogen. Researchers conducted teratogenicity studies using Wistar rats, administering these substances on day 12 of gestation. At equimolar concentrations, DEHP showed the weakest teratogenicity, 2-ethylhexanol showed moderate teratogenicity, and 2-ethylhexanoic acid showed the strongest teratogenicity, consistent with the hypothesis. The similarity in the types of defects caused by these drugs also suggests a common teratogenic mechanism, with 2-ethylhexanoic acid being the primary teratogen.
After intravenous or oral administration, 2-ethylhexanoic acid is rapidly metabolized to derivatives of mono(2-ethylhexyl) phthalate. …
It has been reported that rats, after hydrolyzing di(2-ethylhexyl) phthalate to mono(2-ethylhexyl) phthalate, further metabolize it to di(2-ethylhexyl) phthalate, penta(2-ethylpentyl) phthalate, penta(2-ethylhexyl) phthalate, and di(2-ethylhexyl) phthalate.
Unlike rats, African green monkeys and ferrets excrete metabolites of di(2-ethylhexyl) phthalate in their urine; these metabolites are glucuronide derivatives of mono(2-ethylhexyl) phthalate. Glucuronization appears to occur at the free carboxyl group, while the 2-ethylhexyl substituent is oxidized to an alcohol. For more complete metabolite/metabolite data on di(2-ethylhexyl) phthalate (41 metabolites in total), please visit the HSDB record page. Di(2-ethylhexyl) phthalate (DEHP) is primarily absorbed through ingestion. It is hydrolyzed in the small intestine and absorbed as monoethylhexyl phthalate (MEHP) and 2-ethylhexanol, which may then be distributed to adipose tissue and the kidneys. MEHP is further metabolized through various oxidative reactions, producing more than 30 metabolites, some of which can be conjugated with glucuronic acid and excreted. The oxidation of 2-ethylhexanol primarily produces 2-ethylhexanoic acid and several keto acid derivatives. Most DEHP metabolites are excreted in the urine as glucuronide conjugates, while unmetabolized DEHP is excreted in the feces. (L181)

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Biological Half-Life
The levels of DEHP and di(2-ethylhexyl) phthalate (MEHP) in the plasma of newborns undergoing exchange transfusion have been investigated. In one study, the half-life of MEHP was the same as that of DEHP (approximately 12 hours), indicating that the hydrolysis of DEHP is the rate-limiting metabolic step. However, in other children, the half-life of MEHP was longer than that of DEHP…
Following intravenous injection of radiolabeled DEHP, at least two radioactive elimination phases were observed in rat blood, with short half-lives (4.5–9 minutes and 22 minutes, respectively)... After 7 weeks of oral administration, the elimination phase in the liver was significantly slowed, with a half-life of 3–5 days... No accumulation of DEHP or MEHP was observed when the dose was 2.8 g/kg/day for 7 days... In long-term (5–7 weeks) feeding studies, no accumulation was also observed when the feed dose was 1 or 5 g/kg (equivalent to approximately 50 and 250 mg/kg body weight per day)...
...The mean plasma elimination half-lives of MEHP in 25, 40, and 60-day-old Sprague-Dawley rats were 3.9, 3.1, and 2.8 hours, respectively. ...
Two healthy male volunteers (aged 47 and 34) received a single dose of 30 mg di(2-ethylhexyl) phthalate (purity >99%), or 10 mg di(2-ethylhexyl) phthalate daily for four consecutive days... The estimated urinary elimination half-life was approximately 12 hours. ...
For more complete data on the biological half-lives of di(2-ethylhexyl) phthalate (9 types in total), please visit the HSDB records page.

[1]. Di-2-ethylhexyl phthalate (DEHP) induces apoptosis and autophagy of mouse GC-1 spg cells. Environ Toxicol. 2020 Feb;35(2):292-299.

[2]. Effects of di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis in C3H/N mice. Environ Health Perspect. 2012 Aug;120(8):1123-9.

Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical commonly added to plastics to increase their flexibility. DEHP is a colorless liquid and almost odorless. It is found in a wide variety of plastic products, such as wallpaper, tablecloths, floor tiles, furniture upholstery, shower curtains, garden hoses, swimming pool liners, raincoats, baby pants, dolls, certain toys, shoes, car interiors and headliners, packaging films and sheets, wire and cable sheathing, medical catheters, and blood bags. According to an independent committee of scientific and health experts, DEHP may be carcinogenic. It may also cause developmental toxicity and male reproductive toxicity, according to the National Institute for Occupational Safety and Health (NIOSH) and the Food and Drug Administration (FDA). Di(2-ethylhexyl) phthalate is a colorless to pale yellow oily liquid and is almost odorless. (US Coast Guard, 1999)
Di(2-ethylhexyl) phthalate is a phthalate ester, a di(2-ethylhexyl) ester of phenyl-1,2-dicarboxylic acid. It has functions as an inhibitor of apoptosis, an androstane receptor agonist, and a plasticizer. It is a phthalate ester and diester.
Di(2-ethylhexyl) phthalate has been reported to be found in Penicillium olsenii, Streptomyces, and other organisms with relevant data.
Di(2-ethylhexyl) phthalate is a colorless, oily organic carcinogen with a slight odor. Di(2-ethylhexyl) phthalate is primarily used as a plasticizer in the manufacture of flexible materials for many household products. Inhalation, ingestion, and skin contact are its main potential routes of exposure. Animal studies have shown that exposure to di(2-ethylhexyl) phthalate is associated with an increased incidence of hepatocellular carcinoma. This substance is reasonably expected to be a human carcinogen. (NCI05)
Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical commonly added to plastics to increase their flexibility. Exposure to DEHP is generally low and harmless, but increased exposure through intravenous fluid infusion via plastic tubing or ingestion of contaminated food or water can have toxic effects. This is particularly concerning because DEHP is known to leach into liquids that come into contact with DEHP-containing plastics. (L181, L182)
Phytrates. These are light-colored, odorless liquids used as plasticizers in a variety of resins and elastomers.

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Mechanism of Action
…1000 mg/kg body weight of MEHP (purity >97%) was dissolved in corn oil and administered by gavage to 5-week-old Sprague-Dawley rats, 28-day-old wild-type C57CL/6 mice, or 28-day-old gld mice. GLD mice express a dysfunctional fasL protein that fails to bind to the fas receptor to initiate apoptosis. Following MEHP exposure, apoptosis primarily occurred in spermatocytes in both wild-type and GLD mice. In wild-type mice, germ cell apoptosis significantly increased 6 to 48 hours after MEHP exposure. Apoptotic activity peaked between 12 and 24 hours, representing a 5-fold increase from baseline. In GLD mice, apoptotic levels were approximately 2-fold higher than baseline at 12 and 48 hours after MEHP exposure. Apoptotic activity returned to baseline levels in both groups at 96 hours post-exposure. Western blot analysis showed that fas expression was significantly increased (approximately 3-fold) 3 hours after MEHP exposure in wild-type mice. In GLD mice, fas expression did not change significantly after MEHP exposure. DR4, DR5, and DR6 proteins (fas-independent death receptors in the tumor necrosis factor (TNF) superfamily) were expressed in both wild-type and gld mice, but MEHP exposure did not increase the expression of DR4, DR5, and DR6 proteins in either strain. In the testes of Sprague-Dawley rats, DR5 expression was significantly increased (approximately 1.5-fold) at 1.5 and 3 hours after MEHP exposure, while DR4 expression remained largely unchanged. The precursor caspase 8 cleavage product, a downstream receptor-mediated signaling molecule of the apoptosis pathway, was detected in the testes of both wild-type and gld mice, but its expression was significantly increased only 6 hours after MEHP exposure in gld mice. Electrophoretic mobility shift analysis indicated that DNA binding of NF-κB (a receptor-mediated downstream signaling molecule that may be involved in cell death or survival) was generally reduced in wild-type mice, but NF-κB expression was upregulated in gld mice after MEHP exposure. The conclusion is that these findings suggest that germ cell-associated death receptors and their downstream signaling products appear to respond to MEHP-induced cell damage. Sprague-Dawley male rats were orally administered 250, 500, or 750 mg/kg/day of di(2-ethylhexyl) phthalate (DEHP) for 28 days, while control rats were given corn oil. Western blotting was used to analyze the levels of cell cycle regulators (pRb, cyclins, CDK, and p21) and apoptosis-related proteins. The roles of peroxisome proliferator-activated receptor γ (PPAR-γ), scavenger receptor type B 1 (SR-B1), and ERK1/2 were further investigated to explore the signaling pathways of DEHP-induced apoptosis. The results showed that in rats treated with 500 and 750 mg/kg/d DEHP, the levels of pRB, cyclin D, CDK2, cyclin E, and CDK4 were significantly decreased, while the level of p21 was significantly increased. DEHP exposure led to a dose-dependent increase in the expression of PPAR-γ and RXRα proteins in the testes, while significantly decreasing the expression of RXRγ protein. In addition to PPAR-γ, DEHP also significantly increased the levels of SR-B1 mRNA and phosphorylated ERK1/2 protein. Furthermore, DEHP treatment induced the cleavage of pro-caspase-3 and its substrate, poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner. These data suggest that DEHP exposure may induce the expression of apoptosis-related genes in the testes by inducing PPAR-γ and activating the ERK1/2 pathway. This study employed genome-wide expression profiling combined with gene ontology (GO) and pathway mapping tools to identify affected molecular pathways and processes, and to investigate the acute effects of a non-genotoxic carcinogen and the peroxisome proliferator (PP) dioctyl phthalate (DEHP) in mouse liver (as a model system). Consistent with the known mechanisms of DEHP action, GO analysis of transcriptomic profiling data revealed significant overexpression of genes associated with peroxisome cellular components and those involved in carboxylic acid and lipid metabolism. Furthermore, the study revealed changes in gene expression related to other biological functions such as complement activation, hemostasis, endoplasmic reticulum overload response, and circadian rhythms. These data collectively reveal potential new pathways of action of the peroxisome proliferator-activated receptor (PP) and provide new insights into the mechanisms by which non-genotoxic carcinogens control hepatocyte hypertrophy and proliferation. Peroxisome proliferator-activated receptor α (PPAR-α) is a nuclear receptor belonging to the steroid hormone receptor superfamily; it forms a heterodimer with the retinol X receptor (RXR) and binds to DNA. Peroxisome proliferator response elements (PPREs) have been found in genes of both peroxisomes and microsomal fatty acid oxidases. …Species-specific differences in responses to peroxisome proliferators (e.g., dioctyl phthalate, DEHP), particularly between humans and rats and mice, may be attributed to…PPAR-α expression levels and function, the presence of active PPREs in specific gene promoter regions, and other aspects of interactions with transcriptional regulatory proteins. …Significant species differences exist in PPAR-α mRNA expression in rodent and human livers, with the latter expressing only 1–10% of the levels found in mouse or rat livers. …PPAR-α protein expression levels in human livers are less than 10% of those in mice. …In most human samples studied, PPREs were found to bind primarily to other competing proteins that may block the response to peroxisome proliferators. Furthermore, the levels of PPAR-α protein detected in human livers are lower than estimated by RNA analysis, which can be explained by the finding that a significant portion of PPAR-α mRNA in human livers is missplicing. In 10 human liver samples, truncated PPAR-α mRNA accounted for 25-50% of total PPAR-α mRNA, while no truncated PPAR-α mRNA was detected in rat and mouse livers. The truncated human PPAR-α mRNA expressed in vitro exhibited the following two characteristics: (a) it could not bind to PPRE, a necessary step for gene activation; and (b) it interfered with the gene activation of full-length human PPAR-α, partly because it reduced the level of the coactivator CREB-binding protein, another important component of transcriptional regulation. …The differences in sensitivity to peroxisome proliferators among different species may depend on gene-specific factors. For example, the PPRE promoter region required for transcriptional activation of rodent genes is not present in the promoter regions of human genes… The human liver does not respond significantly to peroxisome proliferation and hepatocyte proliferation induction, which can be explained by multiple aspects of PPAR-α-mediated gene expression regulation… In summary, these findings suggest that the increased incidence of liver tumors in mice and rats treated with di(2-ethylhexyl) phthalate (DEHP) is caused by a mechanism that does not exist in humans.

C24H38O4

390.5561

390.277

117-81-7

117-81-7 DEHP

8343

Colorless to light yellow liquid

1.0±0.1 g/cm3

384.9±10.0 °C at 760 mmHg

-50 °C

207.2±0.0 °C

0.0±0.9 mmHg at 25°C

1.489

8.71

0

4

16

28

394

0

O(C(C1=C([H])C([H])=C([H])C([H])=C1C(=O)OC([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O)C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]

BJQHLKABXJIVAM-UHFFFAOYSA-N

InChI=1S/C24H38O4/c1-5-9-13-19(7-3)17-27-23(25)21-15-11-12-16-22(21)24(26)28-18-20(8-4)14-10-6-2/h11-12,15-16,19-20H,5-10,13-14,17-18H2,1-4H3

bis(2-ethylhexyl) benzene-1,2-dicarboxylate

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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