Di-N-hexyl phthalate

• CAS: 84-75-3
• Catalog Number: ACM84753
• Category: Main Products
• Molecular Weight: 334.45
• Molecular Formula: C₂₀H₃₀O₄
• Synonyms: DIHEXYL PHTHALATE;DI-N-HEXYL PHTHALATE;HEXYL PHTHALATE;PHTHALIC ACID DI-N-HEXYL ESTER;PHTHALIC ACID, BIS-HEXYL ESTER;TIMTEC-BB SBB007740;1,2-Benzenedicarboxylicacid,dihexylester;1,2-benzenedioicaciddihexylester
• IUPAC Name: Dihexyl Phthalate
• Boiling Point: 185-187°C0,5mm
• Melting Point: 65°C
• Flash Point: 185-187°C/0.5mm
• Density: 1,01 g/cm³
• Appearance: colourless liquid
• Exact Mass: 334.21400
• Hazard Statements: Xi
• Packing Group: III
• Safety Description: 26-36/37
• Supplemental Hazard Statements: H360
• Symbol: GHS08

Case Study

Developmental toxicity study and comparison of di-n-hexyl phthalate in rats

Saillenfait, Anne-Marie, Frédéric Gallissot, and Jean-Philippe Sabaté. Journal of applied toxicology 29.6 (2009): 510-521.

The study evaluated the developmental toxicity potential of di-n-hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague-Dawley rats were exposed to doses of 0 (olive oil), 250, 500, and 750 mg kg/day of DnHP or DCHP by gavage at gestational day (GD) 6-20. Maternal food consumption and weight gain were significantly reduced at 750 mg kgp of DnHP and two high doses of DCHP per day. Slight changes in liver weights associated with the induction of peroxisomal enzymes were observed in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including significant embryolethality at 750 mg kg/day, as well as the presence of malformations (mainly cleft palate, eye defects, and axial skeletal abnormalities) and significant reductions in fetal weight at 500 and 750 mg kg/day. A significant delay in ossification and an increased incidence of skeletal variations (e.g., supernumerary lumbar ribs) also occurred at 250 mg kg/d. DnHP showed significant embryolethality and teratogenicity, but DCHP did not. There is evidence that both phthalates can alter the development of the male reproductive system after in utero exposure, with DnHP being more potent than DCHP.
Pregnant rats were given DnHP or DCHP by gavage at 0, 250, 500, or 750 mg/kg/day. Dosing was once daily in the morning on GD 6-20. The dosing volume was 5 ml kg for DnHP and 10 ml kg for DCHP because of its limited solubility in oil. Initial doses were based on GD 6 body weight and adjusted every 3 days throughout treatment. A concurrent control group received vehicle under identical conditions. The dose levels for the final study were based on the results of a pilot study in which pregnant rats (8-12 per group) were dosed with 250, 500, or 750 mg kg/day of DnHP, or 500 or 750 mg kg/day of DCHP. DnHP produced high embryolethality at 750 mg kg/day (46%). Internal examination of viable fetal gonads revealed adverse effects on the male reproductive tract (i.e., undescended testes) at the two high doses of DnHP but not in fetuses in the DCHP-treated group.

Effects of in utero exposure to di-n-hexyl phthalate on reproductive development in male rats

Saillenfait, Anne-Marie, Jean-Philippe Sabaté, and Frédéric Gallissot. Reproductive Toxicology 28.4 (2009): 468-476.

The plasticizer di-n-hexyl phthalate (DnHP) has been shown to be teratogenic, causing adverse effects on the reproductive tract of male rat fetuses. This study was conducted to determine the long-term effects of in utero exposure to DnHP on reproductive development in male offspring. Di-2-ethylhexyl phthalate (DEHP), another phthalate known to disrupt androgen-dependent sexual differentiation in male rats, was used as a positive control. Pregnant Sprague-Dawley rats were given DnHP or DEHP by gavage at 0, 50, 125, 250, or 500 mg DnHP/kg-d and 500 mg DEHP/kg-d on gestational days 12-21. Male offspring exhibited shortened anogenital distance at postnatal day (PND) 1 at 125 mg DnHP/kg-d and above, and areola/retention at 250 and 500 mg DnHP/kg-d before weaning and in adulthood. Severe malformations of the reproductive tract were observed in young adult males at 125 mg DnHP/kg-d and above at necropsy at PND 70-78 or PND 111-120. They mainly included hypospadias, testicular dysgenesis, and undescended testes. Prenatal exposure to DnHP causes permanent and dose-related alterations in reproductive development in male rats.
Pregnant rats were gavaged with 500 mg/kg of DEHP or 50, 125, 250, or 500 mg/kg d of DnHP. Dosing was done once daily in the morning on GD 12 to GD 21, a sensitive period for male reproductive tract differentiation in rats. The dosing volume was 5 ml/kg. The initial dose was based on GD 12 body weight and was adjusted every 3 days throughout the treatment period. The control group received vehicle under the same conditions. Maternal body weight was monitored during treatment and on postpartum days 1, 4, 7, 14, and 21. The dose of DnHP was based on the results of the prenatal study. A pilot study was also conducted in which 9-12 pregnant rats were administered 625 mg/kg-d of DEHP, or 0, 500, or 625 mg/kg-d of DnHP on GD 12 to GD 21.

Effects of in utero administration of di-n-hexyl phthalate on histopathological changes in rat liver tissue

Aydemir, Duygu, et al. Frontiers in Endocrinology 14 (2023): 1128202.

Phthalates are widely used as plasticizers in industry. Phthalates exert endocrine disrupting and peroxisome proliferating effects in humans and wildlife and are implicated in the pathogenesis of various diseases. Serum biochemical parameters, hematological markers, histopathological changes, and oxidative and pentose phosphate pathway (PPP) metabolism in the liver were evaluated in male and female rats after in utero administration of DHP and DCHP, respectively. Dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP) levels were increased, and triglyceride, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels were impaired. Histopathological changes, including congestion, sinusoidal dilatation, inflammatory cell infiltration, nuclear heat, hepatocyte lysis, and hepatic parenchymal degeneration, were observed in liver samples of both DHP and DCHP dose groups.
Prior to mating of males and females, the estrous cycle stage of female rats was examined. Gestation day 0 (GD0) was assumed. Pregnant rats (dams) were divided into a control group administered with corn oil alone (n = 10) and a treatment group administered with dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP), respectively, prepared in corn oil (n = 60). DHP and DCHP solutions were prepared daily and adjusted to the body weight of each rat, with a dose of 0.25 ml per group. The doses of DHP and DCHP were selected not to exceed the acute oral median lethal dose, which is 29.6 mg/kg/day for DHP and >40 g mg/kg/day for DCHP in rats. The low dose level was determined based on the no observed adverse effect level.

Study of di-n-hexyl phthalate in flexible vinyl formulations

Kozlowski, Richard R., and Thomas K. Gallagher. Journal of Vinyl and Additive Technology 5.2 (1999): 94-100.

Low molecular weight esters have been available to PVC compound manufacturers for many years. As a compounding ingredient, it provides manufacturing efficiency or some special properties with sufficient durability for many vinyl applications. In many ways, low molecular weight esters are processing aids in the plasticizer family. Di-n-hexyl phthalate (DnHP) is introduced and compared to other phthalates.
Plastics were prepared using 100 parts of dispersion resin, 75 parts of plasticizer di-n-hexyl phthalate, and 2.5 parts of stabilizer liquid barium zinc. The liquid plasticizer and stabilizer were mixed separately by hand, and then 60% of the mixture was added to the resin in the row mixing bowl. The plastisol was mixed at low shear for 20 minutes, stopping to ensure that the ingredients were completely added. The remaining liquid was then added and mixing continued for another 10 minutes. The plastisol was degassed in a desiccator and vacuumed for 30 minutes after the foam collapsed.

Synthetic Use

Upstream Synthesis Route 1

• 84-66-2
• 111-27-3

• 84-75-3

Reference: [1]Zhurnal Fizicheskoj Khimii,1953,vol. 27,p. 713,716
Chem.Abstr.,1954,p. 13

Upstream Synthesis Route 2

• 85-44-9
• 111-27-3

• 84-75-3

Reference: [1]RSC Advances,2014,vol. 4,p. 57297 - 57307
[2]Synthetic Communications,1999,vol. 29,p. 607 - 611
[3]Polyhedron,2019,vol. 173
[4]Organic Preparations and Procedures International,2000,vol. 32,p. 287 - 290
[5]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,2004,vol. 43,p. 1039 - 1043