Dibutyl phthalate (0.001 µg/mL–1000 µg/mL) significantly dysregulates the expression of genes related to the cell cycle and apoptosis in a dose-dependent manner, which is harmful to follicular growth and viability. On the other hand, MBP had no effect on the toxicity of dibutyl phthalate in follicles exposed in vitro [1].

Dibutyl phthalate (200, 400, or 600 mg/kg/day) resulted in weight loss, decreased testosterone and follicle-stimulating hormone levels in the serum, altered testicular LDH, elevated LPO, and enzymatic resistance in mice. Reduced oxidant levels cause histopathological anomalies [2]. It's possible that dibutyl phthalate (6.25, 12.5, 25, 50, 100, and 200 mg/kg) will negatively impact mice's neurobehavioral development [3].

Absorption, Distribution and Excretion
Following oral administration of dibutyl phthalate (DBP), rats and mice rapidly absorb it and excrete it in urine and feces within 48 hours. Peak concentrations in blood (SRP: not DBP itself, but its metabolites), plasma, and various organs occur at 20–30 minutes; concentrations in the liver are higher than in fat and spleen. Following oral administration of DBP, rats excrete 30.6–43.5% in urine and 20.0–22.0% in feces within 24 hours. The amount absorbed by the fetus is approximately the same as that absorbed by adipose tissue. DBP was detected in rat bile after oral administration. …Small doses are completely absorbed through the intestine. Phthalate esters were detected in the blood of individuals who had consumed food that had come into contact with flexible plastics… The level of dibutyl phthalate detected in the blood was significantly higher than before consuming food packaged in plastic… The blood level of dibutyl phthalate was 0.35 ppm… compared to a pre-meal average of 0.02 ppm. For more complete data on the absorption, distribution, and excretion of dibutyl phthalate (25 in total), please visit the HSDB records page. Metabolites/Metabolites: A 36-year-old male (87 kg) ingested two doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP), at a dose of approximately 60 μg/kg. Urine samples were continuously collected for 48 hours after administration to identify and quantify key monoesters and oxidative metabolites. For both DnBP and DiBP, the majority of the dose was excreted within the first 24 hours after administration (92.2% for DnBP and 90.3% for DiBP), with less than 1% excreted in the urine by day 2. In both cases, simple monoesters were the predominant metabolites (84% for MnBP and 71% for MiBP). For DnBP, approximately 8% was excreted as various side-chain oxidative metabolites. For DiBP, approximately 20% was excreted primarily as the oxidative side-chain metabolite 2OH-MiBP, indicating that DiBP is approximately 2.5 times more oxidatively modified than DnBP. All DnBP and DiBP metabolites reached peak concentrations within 2 to 4 hours after exposure, followed by a monotonic decline. For DnBP metabolites, the elimination half-life of MnBP was 2.6 hours; the elimination half-life of oxidative metabolites was expected to be longer (2.9–6.9 hours). For DiBP metabolites, MiBP had the shortest half-life (3.9 hours), while the oxidative metabolites had slightly longer half-lives (4.1 and 4.2 hours). Similar to simple monoesters, these secondary oxidative metabolites are also important biomarkers of phthalate exposure. This study provides basic human metabolic and toxicokinetic data for two phthalates considered to be human reproductive toxicants and confirmed to be widely present in humans. The major metabolites of (14)C-dibutyl phthalate in the urine of rats, guinea pigs, and hamsters are the monoester MBP and its glucuronide. Small amounts of phthalic acid, unmetabolized DBP, and ω and ω-1 oxidation products of MBP are also present. Following a single oral administration of (14)C-dibutyl phthalate to rats, the metabolites detected in urine included phthalic acid, monobutyl phthalate, mono(3-hydroxybutyl) phthalate, and mono(4-hydroxybutyl) phthalate. The main route of excretion of MBP (the major metabolite of DBP) in rodents and humans is urinary excretion. The major metabolite found in mouse urine appears to be butyl phthalate glucuronide… Approximately 45% of MBuP is excreted via bile, but only about 5% via feces, indicating an effective enterohepatic circulation… Bile metabolites of DBP include butyl phthalate, butyl phthalate glucuronide, and oxidized butyl phthalate glucuronide metabolites… It is known that mice excrete higher levels of glucuroninated phthalate metabolites than rats, and primates excrete higher levels of glucuroninated phthalate metabolites than mice…
For more complete metabolite/metabolite data on dibutyl phthalate (21 metabolites in total), please visit the HSDB record page.
Dibutyl phthalate can be absorbed orally, by inhalation, and through the skin. It is rapidly distributed and eliminated from the body. Dibutyl phthalate (Dbutyl phthalate) is primarily metabolized by nonspecific esterases in the gastrointestinal tract. These enzymes hydrolyze a butyl ester bond to generate monobutyl phthalate (n-butyl phthalate), which is the main toxic metabolite. Monobutyl phthalate (n-butyl phthalate) is bound to glucuronic acid by glucuronidase and excreted in the urine. (L133)

---

Biological half-life
Systemic (animal studies): Almost all are excreted within 48 hours; [TDR, page 473]

Toxicity Summary
Identification and Uses: Dibutyl phthalate (DBP) is a colorless to pale yellow oily liquid. It is used as a plasticizer; a solvent for oil-soluble dyes, pesticides, and other organic compounds; an antifoaming agent; a textile fiber lubricant; a fragrance fixative; and an insect repellent. Human Contact and Toxicity: DBP appears to have minimal skin or eye irritation and is unlikely to cause allergic reactions. A few cases of allergic reactions following exposure to DBP have been reported in humans. In vitro studies have shown that human skin permeability to this compound is lower than that of rat skin. One case described involved a chemical plant worker who accidentally ingested approximately 10 grams of DBP. Delayed signs and symptoms included nausea, vomiting, and dizziness, followed by headache, eye pain and irritation, tearing, photophobia, and conjunctivitis. Full recovery occurred within two weeks. There is evidence that DBP has a mild effect on the kidneys, likely due to the systemic hydrolysis of esters and the cumulative effect of alcohols and acids and their oxidation and decomposition products. A recent report described an increased incidence of hypospadias (p<0.05), cryptorchidism (p<0.05), and breast cancer (p<0.05) in the children of New Zealand soldiers who served in Malaya (1948–1960). These soldiers applied DBP to their clothing daily as a mite repellent to prevent tick-borne jungle typhus. Another study showed that high concentrations of DBP exposure were associated with earlier pubic hair development in boys. In human leukocyte cultures, DBP exposure did not cause chromatid aberrations. DBP induced the proliferation of estrogen-responsive breast cancer cell lines MCF-7 and ZR-75. Animal studies: The effects of dibutyl phthalate (DBP) exposure were similar to other phthalates, causing hepatomegaly, increased hepatic peroxisome count, fetal toxicity, teratogenicity, and testicular damage in susceptible species. DBP showed low acute toxicity in rats and mice. Acute toxicity symptoms in laboratory animals included decreased activity, dyspnea, and impaired motor coordination. Short-term repeated-dose toxicity studies have shown that oral administration of DBP to rats resulted in peroxisome proliferation and hepatomegaly. Long-term studies have shown that rats experienced slower weight gain, increased relative liver weight, peroxisome proliferation accompanied by enhanced peroxisome enzyme activity, as well as altered testicular enzymes and testicular germ cell degeneration. The effects of DBP exposure on the testes exhibit significant species variability, with minimal effects observed in mice and hamsters. In continuous breeding protocols, results showed that animals exposed to dibutyl phthalate (DBP) during development and maturation experienced more significant adverse effects than those exposed only in adulthood. DBP typically induces fetal toxicity without maternal toxicity. Existing data also indicate that high doses of DBP are teratogenic, and teratogenic sensitivity varies with developmental stage and time of administration. DBP is not genotoxic. Because DBP can cause peroxisome proliferation, it may be a rodent liver carcinogen, although its ability to induce hepatomegaly and peroxisome proliferation is far weaker than that of dioctyl phthalate (DEH). In rats, after DBP ingestion, it is primarily metabolized in the small intestine by nonspecific esterases to produce dibutyl phthalate (DBP), with limited subsequent biochemical oxidation of its alkyl side chain. DBP is stable and does not readily undergo hydrolysis of the second ester group. DBP and other metabolites are mainly excreted in the urine as glucuronide conjugates. Ecotoxicity studies: Currently, the average concentration of DBP in surface water poses a low risk to aquatic organisms. However, in heavily polluted rivers, the safe range is much smaller. Recent data show that female adult Murray rainbowfish exposed to subacute concentrations of DBP for seven consecutive days exhibit anti-estrogenic effects. A three-week experiment examined eggs of the ring-necked dove (Streptophelia risoria) fed with DBP. The results showed a 10% reduction in eggshell thickness and a 23% increase in permeability. Dibutyl phthalate (DBP) vapors exposed to light interfere with the synthesis of carotenoids in green plants, leading to chlorophyll deficiency. In extreme cases, leaves completely lose chlorophyll and turn white. The most typical toxic effect of DBP is testicular atrophy. DBP exposure causes the release of iron from hemoglobin and/or transferrin in the liver and spleen, resulting in iron depletion in the blood and testes. Reduced available iron leads to decreased succinate dehydrogenase activity in Sertoli cells. This disrupts the energy transfer system between Sertoli cells and germ cells, which is crucial for male germ cell differentiation, passage through the seminiferous epithelium, and eventual release into mature sperm. DBP may also have weak estrogenic activity. Studies have shown that it can exert toxic effects on liver mitochondria by uncoupling energy-related processes and inhibiting succinate dehydrogenase. (L133, A105)

---

Toxicity Data
LC50 (mice) = 25,000 mg/m3/2H
LD50: 3050 mg/kg (intraperitoneal injection, rat) (T13)
LD50: 720 mg/kg (intravenous injection, mouse) (T13)
LD50: 5289 mg/kg (oral administration, mouse) (T13)
LC50: 25 g/m3/2 hours (inhalation, mouse) (T13)

---

Interactions
Antagonistic effects were observed when di(2-ethylhexyl) phthalate or dibutyl phthalate was co-administered with 21 organophosphates in houseflies.
Dibutyl phthalate was applied topically or injected into female houseflies at a concentration of 20 μg/fly. (1000 μg/g body weight) Non-toxic, mortality rate less than 16% after 24 hours… Antagonistic effects were observed when fruit flies were simultaneously treated with dibutyl phthalate (DBP) and various organophosphate insecticides; however, synergistic effects were observed when fruit flies were pretreated with phthalates 30 minutes before insecticide exposure. DBP inhibited the metabolism of organophosphate insecticides, which explains the synergistic effect. When phthalates and insecticides were applied simultaneously, DBP led to an increase in the total lipophilic pool, which may have kept the in vivo concentration of insecticides below the toxicity threshold. …The absorption of dimethyl phthalate, di-n-butyl phthalate, and di(2-ethylhexyl) phthalate was studied using rat small intestinal intestinal sac preparations. Monoesters were absorbed faster than their corresponding diesters. Esterases in the mucosal epithelium hydrolyzed the diesters into monoesters during absorption. The absorption of dibutyl phthalate was significantly reduced when esterases were inhibited by organophosphates. This study aimed to investigate the relationship between atopic hypersensitivity and depression, and the role of dibutyl phthalate in the development of depression. BALB/c mice were randomly divided into eight groups: saline group; ovalbumin (OVA) immunization group; saline + dibutyl phthalate (0.45 mg/kg/d) group; saline + dibutyl phthalate (45 mg/kg/d) group; ovalbumin (OVA) immunization + dibutyl phthalate (0.45 mg/kg/d) group; ovalbumin (OVA) immunization + dibutyl phthalate (45 mg/kg/d) group; saline + hydrocortisone (30 mg/kg/d) group; and ovalbumin (OVA) immunization + hydrocortisone (30 mg/kg/d) group. Behavioral parameters (e.g., open field test, tail suspension test, and forced swimming test), visceral coefficients (brain and spleen), oxidative damage parameters [e.g., reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH)], and IgE and IL-4 levels were subsequently analyzed. In both the saline and OVA groups, the severity of depressive symptoms in mice increased with increasing DBP concentration. Furthermore, compared to the saline group at the same exposure concentration, the OVA-immunized group exhibited more severe depressive behavior. Oxidative damage was dose-dependently associated with increasing DBP concentration in all groups. IL-4 and IgE levels were associated with low-dose DBP stimulation, but this stimulatory effect shifted to high-dose inhibition with increasing DBP exposure, likely due to spleen damage caused by high DBP concentrations. The occurrence of atopic hypersensitivity may increase the risk of depression in mice, and dibutyl phthalate (DBP) appears to contribute to the role of ovalbumin (OVA) in this model. For more complete data on interactions of dibutyl phthalate (10 in total), please visit the HSDB record page.

---

Non-human toxicity values
Rat intraperitoneal LD50: 3050 mg/kg
Mouse inhalation LC50: 25 g/m³/2 hr
Mouse intravenous LD50: 720 mg/kg
Mouse oral LD50: 5289 mg/kg. For more complete data on non-human toxicity of dibutyl phthalate (16 in total), please visit the HSDB record page.

[1]. Effects of in vitro exposure to dibutyl phthalate, mono-butyl phthalate, and acetyl tributyl citrate on ovarian antral follicle growth and viability. Biol Reprod. 2017 May 1;96(5):1105-1117.

[2]. Dibutyl phthalate induces oxidative stress and impairs spermatogenesis in adult rats. Toxicol Ind Health. 2016 Aug;32(8):1467-1477.

[3]. Determination of dibutyl phthalate neurobehavioral toxicity in mice. Food Chem Toxicol. 2016 Aug;94:221-6.

Therapeutic Uses
Scrub typhus is a rickettsial disease caused by the larvae of the mite Deschus trichomonas. Due to the increased risk of infection during exercise/wartime travel to mite-endemic areas, scrub typhus is of particular importance for armed forces personnel. The best way to prevent this disease is through personal protective measures, including the use of insect repellents. This study aimed to determine the relative efficacy of the insect repellents diacetamide (DEET), dibutyl phthalate (DBP), and a domestically produced insect repellent, diethylphenylacetamide (DEPA), against Deschus trichomonas larvae. The residues of these repellents on impregnated fabrics before, after, and after ironing were tested using a specially designed test kit. The acaricidal efficacy of the treated fabrics was evaluated, and the topical application of the repellents in mice was assessed using a novel animal model. The study found that DEET and DEPA provided the best protection (repellent and acaricidal efficacy), with impregnated uniforms able to withstand two washes, and topical application (8 hours) showing better results. Ironing significantly reduces the repellent efficacy of DEET and dibutyl phthalate (DBP). The results of this study indicate that DEPA and DEET are superior to other methods in both uniform soaking and topical application, and can be used to prevent scrub typhus in the military.

C16H22O4

278.35

278.151

84-74-2

Dibutyl phthalate-3,4,5,6-d4;93952-11-5;Dibutyl phthalate-d22;358731-15-4

3026

Colorless to light yellow liquid

1.1±0.1 g/cm3

337.0±10.0 °C at 760 mmHg

-35 °C

171.1±0.0 °C

0.0±0.7 mmHg at 25°C

1.499

4.82

0

4

10

20

271

0

O=C(C1C(C(OCCCC)=O)=CC=CC=1)OCCCC

DOIRQSBPFJWKBE-UHFFFAOYSA-N

InChI=1S/C16H22O4/c1-3-5-11-19-15(17)13-9-7-8-10-14(13)16(18)20-12-6-4-2/h7-10H,3-6,11-12H2,1-2H3

dibutyl benzene-1,2-dicarboxylate

NSC6370; NSC-6370; NSC 6370

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 :≥ 50 mg/mL (~179.64 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% EtOH + 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 25.0 mg/mL clear EtOH 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% EtOH + 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 25.0 mg/mL clear EtOH 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (8.98 mM) (saturation unknown) in 10% EtOH + 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 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

---

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