Absorption, Distribution and Excretion
When administered either IV or orally ... it is mainly excreted in urine and bile.
It appeared to be rapidly cleared from blood, most being removed within 5-7 hr of completion of dialysis.
In one study of subjects who received hemodialysis, blood transfusions or blood that had previously been in contact with polyvinyl chloride medical products, di(2-ethylhexyl) phthalate was found at the following levels (ug/g wet tissue): brain (1.9), heart (0.5), kidney (1.2-2.2), liver (1.5-4.6), lung (1.4-2.2) & spleen (2.2-4.7).
The levels of di(2-ethylhexyl) phthalate in neonatal heart tissue from infants who had undergone umbilical catheterization, either alone or with admin of blood products, were reported to be higher than those in similar tissue from untreated infants.
For more Absorption, Distribution and Excretion (Complete) data for BIS(2-ETHYLHEXYL) PHTHALATE (67 total), please visit the HSDB record page.

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Metabolism / Metabolites
It is hypothesized that the teratogen di(2-ethylhexyl) phthalate (DEHP) acts by in vivo hydrolysis to 2-ethylhexanol (2-EXHO), which in turn is metabolized to 2-ethylhexanoic acid (2-EXHA), the proximate teratogen. Teratological studies were conducted with Wistar rats, with administration of these agents on day 12 of geatation. On an equimolar basis DEHP was least potent, 2-ethylhexanol was intermediate, and 2-ethylhexanoic acid was the most potent of the three agents, which is consistent with the hypothesis. Similarity in the types of defects found with these agents also suggests a common mechanism, with 2-ethylhexanoic acid as the proximate teratogen.
When admin either iv or orally, it is rapidly metabolized to derivatives of mono-(2-ethylhexyl)-phthalate. ...
Rats have been reported to metabolize di(2-ethylhexyl) phthalate to 5-keto-2-ethylhexyl phthalate, 5-carboxyl-2-ethylpentyl phthalate, 5-hydroxy-2-ethylhexyl phthalate & 2-carboxymethylbutyl phthalate after initial hydrolysis to mono(2-ethylhexyl) phthalate.
African green monkeys & ferrets, in contrast to rats, excrete di(2-ethylhexyl) phthalate metabolites in urine as glucuronide derivatives of mono(2-ethylhexyl) phthalate. Glucuronidation appears to occur at the free carboxyl group, while 2-ethylhexyl substituent is oxidized to an alcohol.
For more Metabolism/Metabolites (Complete) data for BIS(2-ETHYLHEXYL) PHTHALATE (41 total), please visit the HSDB record page.
DEHP is mainly absorbed via ingestion. It is hydrolyzed in the small intestine and absorbed as monoethylhexylphthalate (MEHP) and 2-ethylhexanol, then likely distributed to the adipose tissues and kidneys. MEHP is further metabolized via numerous oxidative reactions, resulting in the formation of 30 or more metabolites, some of which can be conjugated with glucuronic acid for excretion. Oxidation of 2-ethylhexanol primarily yields 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 faeces. (L181)

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Biological Half-Life
The levels of DEHP and MEHP in plasma have been studied in newborn infants given blood exchange transfusions. In one case the MEHP half-life was the same as for DEHP (about 12 hr), indicating that the hydrolysis of DEHP was the rate-limiting metabolic step. However, in other children the half-time of MEHP was longer than that of DEHP ... .
After the iv admin of radiolabelled DEHP, at least two elimination phases of radioactivity, with short half-lives (4.5-9 and 22 min, respectively), were observed in rat blood ... After 7 wk of oral admin, the elimination phase in the liver was considerably slower, the half-life being 3-5 days ... No accumulation of DEHP or MEHP was observed when the dosage was 2.8 g/kg/day for 7 days ... nor was there any in a long-term (5-7 weeks) feeding study at a dose level of 1 or 5 g/kg diet (corresponding to a daily dose of about 50 and 250 mg/kg bw) ... .
... The mean plasma elimination halflives of MEHP were 3.9, 3.1 and 2.8 hours, respectively for 25, 40 and 60 days old /Sprague-Dawley/ rats. ...
Two healthy male volunteers (47 and 34 years old) received 30 mg DEHP (> 99% pure) as a single dose or 10 mg/day of DEHP for 4 days ... A urinary elimination half-life of about 12 hours was estimated. ...
For more Biological Half-Life (Complete) data for BIS(2-ETHYLHEXYL) PHTHALATE (9 total), please visit the HSDB record 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) phthlate (DEHP) is a manufactured chemical that is commonly added to plastics to make them flexible. DEHP is a colorless liquid with almost no odor. DEHP is present in plastic products such as wall coverings, tablecloths, floor tiles, furniture upholstery, shower curtains, garden hoses, swimming pool liners, rainwear, baby pants, dolls, some toys, shoes, automobile upholstery and tops, packaging film and sheets, sheathing for wire and cable, medical tubing, and blood storage bags.
Di(2-ethylhexyl)phthalate (DEHP) can cause cancer according to an independent committee of scientific and health experts. It can cause developmental toxicity and male reproductive toxicity according to NIOSH and the FDA.
Di(2-ethylhexyl) phthalate is a colorless to pale yellow oily liquid. Nearly odorless. (USCG, 1999)
Bis(2-ethylhexyl) phthalate is a phthalate ester that is the bis(2-ethylhexyl) ester of benzene-1,2-dicarboxylic acid. It has a role as an apoptosis inhibitor, an androstane receptor agonist and a plasticiser. It is a phthalate ester and a diester.
Bis
Bis(2-ethylhexyl) phthalate has been reported in Penicillium olsonii, Streptomyces, and other organisms with data available.
Diethylhexylphthalate is a colorless, oily organic carcinogen with a slight odor. Bis(2-Ethylhexyl) Phthalate is mainly used as a plasticizer for fabricating flexible materials for many household products. Inhalation, digestion, and dermal contact are the primary routes of potential exposure, which was linked to increased incidence of hepatocellular carcinomas in animals. This substance is reasonably anticipated to be a human carcinogen. (NCI05)
Di(2-ethylhexyl) phthlate (DEHP) is a manufactured chemical that is commonly added to plastics to make them flexible. DEHP exposure is generally low and not harmful, but increased exposures resulting from intravenous fluids delivered through plastic tubing or ingesting contaminated foods or water may have toxic effects. This is of particular concern since DEHP is known to leach into liquid that come in contact with DEHP containing plastic. (L181, L182)
An ester of phthalic acid. It appears as a light-colored, odorless liquid and is used as a plasticizer for many resins and elastomers.

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Mechanism of Action
... A single dose of 1000 mg/kg bw MEHP (> 97% purity) in corn oil was administered by gavage to 5-week-old Sprague-Dawley rats, 28-day-old wild-type C57CL/6 mice, or 28-day-old gld mice. The gld mice express a dysfunctional fasL protein, which cannot bind to the fas receptor to initiate apoptosis. ... Following MEHP exposure, apoptosis was found to occur primarily in spermatocytes in both wild-type and gld mice. In wild-type mice, germ cell apoptosis was significantly increased from 6 to 48 hours following MEHP exposure. Apoptotic activity peaked between 12 and 24 hours with 5-fold increases compared to baseline levels. A significant ~2-fold increase in apoptosis compared to baseline levels was observed at 12 and 48 hours following MEHP exposure of gld mice. In both groups of mice, apoptotic activity returned to baseline levels by 96 hours following exposure. Western blot analyses revealed that fas expression significantly increased in wild-type mice (~ 3-fold) at 3 hours following MEHP exposure. There was no significant alteration in fas expression following MEHP exposure in gld mice. Expression of DR4, DR5, and DR6 proteins /which are fas-independent death receptors in the tumor necrosis factor (TNF) superfamily/ occurred in both wild-type and gld mice, but MEHP exposure did not increase expression in either strain. DR5 but not DR4 expression significantly increased in Sprague-Dawley rat testes (~1.5-fold) at 1.5 and 3 hours following MEHP exposure. Procaspase 8 cleavage products, downstream receptor-mediated signals of apoptotic pathways, were detected in testes of wild-type and gld mice, but expression was significantly increased only in gld mice at 6 hours following MEHP exposure. Electrophoretic mobility shift assays demonstrated that DNA binding of NFkappa3, a receptor-mediated downstream signal possibly involved in cell death or survival, was generally reduced in wild-type mice but upregulated in gld mice following MEHP exposure. ... /It was/ concluded that these findings demonstrate that germ-cell related death receptors and downstream signaling products appear to respond to MEHP-induced cell injury ... /MEHP/
Sprague-Dawley male rats were treated orally with 250, 500, or 750 mg/kg/d Di(2-ethylhexyl) phthalate (DEHP) for 28 days, while control rats were given corn oil. The levels of cell cycle regulators (pRb, cyclins, CDKs, and p21) and apoptosis-related proteins were analyzed by Western blot analysis. The role of PPAR-gamma (PPAR-gamma), class B scavenger receptor type 1 (SR-B1), and ERK1/2 was further studied to examine the signaling pathway for DEHP-induced apoptosis. Results showed that the levels of pRB, cyclin D, CDK2, cyclin E, and CDK4 were significantly lower in rats given 500 and 750 mg/kg/d DEHP, while levels of p21 were significantly higher in rat testes. Dose-dependent increases in PPAR-gamma and RXRalpha proteins were observed in testes after DEHP exposure, while there was a significant decrease in RXRgamma protein levels. In addition to PPAR-gamma, DEHP also significantly increased SR-B1 mRNA and phosphorylated ERK1/2 protein levels. Furthermore, DEHP treatment induced pro-caspase-3 and cleavage of its substrate protein, poly(ADP-ribose) polymerase (PARP), in a dose-dependent manner. Data suggest that DEHP exposure may induce the expresson of apoptosis-related genes in testes through induction of PPAR-gamma and activation of the ERK1/2 pathway.
Global gene expression profiling combined with an evaluation of Gene Ontology (GO) and pathway mapping tools /was used/ ... for identifying the molecular pathways and processes affected /to examine/ ... the acute effects caused by the non-genotoxic carcinogen and peroxisome proliferator (PP) diethylhexylphthalate (DEHP) in the mouse liver as a model system. Consistent with what is known about the mode of action of DEHP, /the/ GO analysis of transcript profiling data revealed a striking overrepresentation of genes associated with the peroxisomal cellular component, together with genes involved in carboxylic acid and lipid metabolism. Furthermore ... gene expression changes associated with additional biological functions, including complement activation, hemostasis, the endoplasmic reticulum overload response, and circadian rhythm /were revealed/. Together, these data reveal potential new pathways of PP action and shed new light on the mechanisms by which non-genotoxic carcinogens control hepatocyte hypertrophy and proliferation. ...
... Peroxisome proliferator-activated receptor alpha (PPAR-alpha), the nuclear receptor, is a member of the steroid hormone receptor superfamily and binds to DNA as a heterodimer with the retinoid X receptor (RXR). Peroxisome proliferator response elements (PPREs) have been found in genes for both peroxisomal and microsomal fatty acid-oxidizing enzymes. ... The species differences /responding to peroxisome proliferators, eg DEHP/, particularly with respect to humans compared to rats and mice, can be potentially attributed to ... the level of expression and functional capability of PPAR-alpha, the presence or absence of active PPREs in the promoter region of specific genes, and other aspects of interaction with transcriptional regulatory proteins. ... Marked species differences in the expression of PPAR-alpha mRNA have been demonstrated between rodent and human liver, with the latter expressing 1-10% of the levels found in mouse or rat liver ... PPAR-alpha protein expression /in human livers/ contained less than 10% of the level in mice. ... In most human samples studied, it was found that PPREs are mainly bound by other competing proteins that may block peroxisome proliferator responsiveness. In addition, the low levels of PPAR-alpha protein detected in human liver were lower than those estimated from RNA analysis and this was explained by the finding that a significant fraction of PPAR-alpha mRNA is mis-spliced in human liver. ... The truncated PPAR-alpha mRNA accounted for 25-50% of total PPAR-alpha mRNA in 10 human liver samples, while no truncated PPAR-alpha mRNA was found in livers of rats and mice. The truncated human PPAR-alpha mRNA was expressed in vitro, where it was shown to (a) fail to bind to PPRE, a necessary step for gene activation and (b) interfere with gene activation by expressed full-length human PPAR-alpha, in part due to titration of coactivator CREB-binding protein, an additional element of transcriptional regulation. ... Differential species sensitivity to peroxisome proliferators could depend on gene-specific factors. In the case of peroxisomal acyl-coenzyme A oxidase, the promoter regions containing PPRE responsible for transcriptional activation of the rodent gene are not present in the promoter region of the human gene ... The absence of a significant response of human liver to induction of peroxisome proliferation and hepatocellular proliferation is explained by several aspects of PPAR-alpha-mediated regulation of gene expression. ... Overall, these findings indicate that the increased incidence of liver tumors in mice and rats treated with di(2-ethylhexyl) phthalate results from a mechanism that does not operate 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.)