DEHP targets multiple organ systems including the eyes, respiratory system, central nervous system, liver, reproductive system, and gastrointestinal tract. The compound has been implicated in obesity and insulin resistance. DEHP inhibits prostaglandin synthesis and adversely affects the endocrine system. The developing fetus and male reproductive system are particular targets of DEHP toxicity. As an endocrine disruptor, DEHP interferes with hormone signaling, particularly affecting reproductive and developmental processes. The compound also has effects on liver function and metabolism.

In vitro studies demonstrate that DEHP exhibits a diverse range of bioactivities. The compound inhibits prostaglandin synthesis and adversely affects the endocrine system. DEHP has been shown to have effects on cell signaling pathways related to metabolism and hormone function. In cellular assays, DEHP can disrupt normal cellular function and gene expression related to lipid metabolism and hormone signaling. The compound's effects on cell proliferation and differentiation have been studied in various cell types.

In vivo studies show that DEHP has significant toxicological effects in animal models. Orally administered DEHP produces significant dose-related increases in liver tumor responses in rats and mice of both sexes. DEHP has oral toxicity during pregnancy and suckling in the Long-Evans rat. The compound can induce antiandrogenic effects in Sprague-Dawley (SD) rats. DEHP exposure is associated with reproductive and developmental toxicity, including effects on male reproductive system development and function. The compound has also been linked to obesity and insulin resistance in animal models.

In vitro enzyme/receptor binding assays for DEHP involve measuring effects on various molecular targets. The compound's effects on prostaglandin synthesis are assessed by measuring prostaglandin E2 (PGE2) production in cells treated with DEHP. Endocrine disruption is evaluated using reporter gene assays for estrogen receptor, androgen receptor, and other nuclear receptors. PPARγ activation is measured using PPARγ reporter assays. The compound's binding to hormone receptors is assessed using radioligand binding assays. Effects on enzyme activity (e.g., cytochrome P450 enzymes) are measured using specific substrates and product quantification. IC50/EC50 values are determined from dose-response curves.

In vitro cellular assays for DEHP typically use various cell lines including hepatocytes, adipocytes, reproductive cells, and endocrine cells. Cells are cultured in appropriate media and treated with the compound at concentrations of 0.1-1000 μM for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays. Hormone receptor activity is measured using reporter gene assays. Prostaglandin synthesis is measured by ELISA. Lipid accumulation is assessed by Oil Red O staining. Gene expression changes (PPARγ, SREBP, etc.) are analyzed by qPCR and Western blot. Oxidative stress is measured using ROS detection probes.

In vivo animal studies for DEHP involve oral administration to rats and mice at various doses. Long-term studies (2 years or more) assess carcinogenicity, with liver tumor responses being a key endpoint. Reproductive and developmental toxicity studies involve exposure during pregnancy and lactation, with effects on offspring development and reproductive function assessed. Endocrine effects are evaluated by measuring hormone levels, organ weights (testes, prostate, etc.), and histopathological analysis. Metabolic effects are assessed by measuring body weight, glucose tolerance, insulin sensitivity, and lipid profiles.

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.
Pharmacokinetic properties of DEHP indicate that it is absorbed through oral, dermal, and inhalation routes. The compound has a molecular weight of 390.56 and molecular formula of C24H38O4. DEHP is lipophilic and distributes to fatty tissues. It is metabolized in the liver to mono(2-ethylhexyl) phthalate (MEHP) and other metabolites. DEHP and its metabolites are primarily excreted in urine and feces. The compound has a relatively long half-life in the body due to accumulation in adipose tissue. The primary route of human exposure is through diet, particularly contaminated food.

Toxicological data for DEHP indicates significant toxicity concerns. The compound is classified as a probable human carcinogen based on liver tumor increases in rats and mice. DEHP is a reproductive and developmental toxicant, with effects on male reproductive system development and function. The compound is an endocrine disruptor with antiandrogenic effects. DEHP has been implicated in obesity and insulin resistance. Occupational exposure limits have been established for DEHP in many jurisdictions. The compound is regulated as a hazardous substance due to its toxicity and environmental persistence.

[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.
DEHP (di(2-ethylhexyl) phthalate, also known as DOP) is an industrial chemical with CAS number 117-81-7. Its molecular formula is C24H38O4. DEHP is widely used as a plasticizer in PVC products and in various industrial applications. The compound has significant health and environmental concerns due to its endocrine-disrupting effects and toxicity. DEHP is regulated as a hazardous substance and is restricted in many consumer products. It is not approved for therapeutic use and is strictly for research and industrial purposes.

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

Endogenously produced metabolite

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

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO: ~150 mg/mL (~384.1 mM; with ultrasonication) 0.1 M NaOH: ~6.7 mg/mL (~17.1 mM; ultrasonic and warming and adjust pH to 10 with 0.1 M NaOH and heat to 60°C)
H2O: < 0.1 mg/mL (insoluble)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.20 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 (12.5 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: ≥ 1.25 mg/mL (3.20 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 (12.5 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.)