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
Dibutyl phthalate administered orally to rats and mice /was/ rapidly absorbed and excreted in urine and feces within 48 hr. Max concentrations in blood /SRP: not DBP itself but a metabolite/ plasma & various organs /occurred/ at 20-30 min; /concentrations were/ greater in liver than fat and spleen.
Dibutyl phthalate given orally to rats was excreted in urine 30.6-43.5% and in feces 20.0-22.0% in 24 hr. Amounts absorbed by fetuses were approximately /the/ same as by fat tissues.
Dibutyl phthalate was detected in the bile of rats after oral administration. ... A small part of the dose was absorbed intact through the intestine.
The presence of phthalate esters in the blood of individuals /who had/ ingested food /that/ had been in contact with flexible plastics ... dibutyl phthalate levels detected in the blood were much higher than prior to eating the food in the plastic packaging system ... dibutyl phthalate levels in blood /were/ 0.35 ppm ... compared to an average value of 0.02 ppm prior to the meals.
For more Absorption, Distribution and Excretion (Complete) data for DIBUTYL PHTHALATE (25 total), please visit the HSDB record page.

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Metabolism / Metabolites
An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of approximately 60 ug/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hr post-dose. For both DnBP and DiBP, the majority of the dose was excreted in the first 24 hr (92.2 % of DnBP, 90.3 % of DiBP), while only <1 % of the dose was excreted in urine on day 2. In each case, the simple monoesters were the major metabolites (MnBP, 84 %; MiBP, 71 %). For DnBP, approximately 8 % was excreted as various side chain oxidized metabolites. For DiBP, approximately 20 % was excreted mainly as the oxidized side chain metabolite 2OH-MiBP, indicating that the extent of oxidative modification is around 2.5 times higher for DiBP than for DnBP. All DnBP and DiBP metabolites reached peak concentrations between 2 and 4 hr post-exposure, followed by a monotonic decline. For DnBP metabolites, the elimination halftime of MnBP was 2.6 hr; longer elimination halftimes were estimated for the oxidized metabolites (2.9-6.9 hr). For DiBP metabolites, MiBP had the shortest halftime (3.9 hr), and the oxidized metabolites had somewhat longer halftimes (4.1 and 4.2 hr). Together with the simple monoesters, secondary oxidized metabolites are additional and valuable biomarkers of phthalate exposure. This study provides basic human metabolism and toxicokinetic data for two phthalates that have to be considered human reproductive toxicants and that have been shown to be omnipresent in humans.
Main urinary metabolite of (14)C-dibutyl phthalate in the rat, guinea pig and hamster ... the monoester, MBP and its glucuronide. ... small amount of phthalic acid, unchanged DBP and omega and omega-1 oxidation products of MBP.
Metabolites found in rat urine after a single oral dose of (14)C-dibutyl phthalate included: phthalic acid, mono-butyl phthalate, mono-(3-hydroxy-butyl) phthalate, and mono-(4-hydroxy butyl) phthalate.
The primary route of MBuP, the major DBP metabolite, elimination in rodents and humans is urinary excretion. The monobutylphthalate glucuronide appears to be the primary metabolite identified in rat urine ... . MBuP is excreted into the bile (about 45%), but only about 5% is eliminated in the feces, indicating that efficient enterohepatic recirculation occurs ... . Biliary metabolites of DBP include monobutylphthalate, monobutylphthalate glucuronide, and oxidized monobutylphthalate glucuronide metabolites ... . Mice are known to excrete higher amounts of glucuronidated phthalate ester metabolites than rats and primates excrete higher levels of glucuronidated phthalate ester metabolites than mice. ...
For more Metabolism/Metabolites (Complete) data for DIBUTYL PHTHALATE (21 total), please visit the HSDB record page.
Di-n-butyl phthalate is absorbed via oral, inhalation, and dermal routes. It is rapidly distributed and cleared from the body. Metabolism of di-n-butyl phthalate proceeds mainly by nonspecific esterases in the gastrointestinal tract, which hydrolyze of one butyl ester bond to yield mono-n-butyl phthalate, the primary toxic metabolite. Mono-n-butyl phthalate is conjugated with glucuronic acid via glucuronosyltransferase and excreted in the urine. (L133)

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Biological Half-Life
Whole body (animal studies): virtually all eliminated within 48 hours; [TDR, p. 473]

Toxicity Summary
IDENTIFICATION AND USE: Dibutyl phthalate (DBP) is a colorless to faint yellow, oily liquid. It is used as plasticizer; solvent for oil-soluble dyes, insecticides and other organics; antifoam agent; textile fiber lubricant; fragrance fixative; insect repellent. HUMAN EXPOSURE AND TOXICITY: DBP appears to have little potential to irritate skin or eyes or to induce sensitization. In humans, a few cases of sensitization after exposure to DBP have been reported. In vitro studies showed human skin has been found to be less permeable than rat skin to this compound. A case described in which a chemical worker accidentally swallowed about 10 g of DBP. Delayed signs and symptoms included nausea, vomiting, and dizziness, followed later by headache, pain, and irritation in the eyes, lacrimation, photophobia, and conjunctivitis. Complete recovery occurred within 2 wk. There was evidence of a slight effect on the kidney, which may have been the result of systemic hydrolysis of the ester and cumulative effects of the alcohol and the acid, as well as their oxidation and decomposition products. A recent report described increases in the incidences 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) and were exposed to DBP applied daily to their clothing as an acaricide to prevent tick-transmitted bush typhus. In other study high exposure to DBP was associated with earlier age at pubarche in boys. DBP exposure in human leukocyte cultures did not result in chromatid aberrations. DBP induced proliferation in estrogen-responsive breast cancer cell lines MCF-7 and ZR-75. ANIMAL STUDIES: The profile of effects following exposure to DBP is similar to that of other phthalate esters, which, in susceptible species, can induce hepatomegaly, increased numbers of hepatic peroxisomes, fetotoxicity, teratogenicity, and testicular damage. The acute toxicity of DBP in rats and mice is low. Signs of acute toxicity in laboratory animals include depression of activity, labored breathing, and lack of coordination. In short-term repeated-dose toxicity studies, effects in rats after oral administration included peroxisome proliferation and hepatomegaly. In longer-term studies, the effects in rats included reduced rate of weight gain, increase in relative liver weight, peroxisomal proliferation with increased peroxisomal enzyme activity, as well as alteration in testicular enzymes and degeneration of testicular germinal cells of rats. There are considerable species differences in effects on the testes following exposure to DBP, minimal effects being observed in mice and hamsters. In a continuous breeding protocol results suggest that the adverse effects of DBP are more marked in animals exposed during development and maturation than in animals exposed as adults only. DBP generally induces fetotoxic effects in the absence of maternal toxicity. Available data also indicate that DBP is teratogenic at high doses and that susceptibility to teratogenesis varies with developmental state and period of administration. DBP is not genotoxic. Since DBP causes peroxisomal proliferation, it is possible that it might be a rodent liver carcinogen, although it is much weaker in inducing hepatomegaly and peroxisome proliferation than diethylhexyl phthalate. In rats, following ingestion, DBP is metabolized by nonspecific esterases mainly in the small intestine to yield mono-n-butyl phthalate with limited subsequent biochemical oxidation of the alkyl side chain. Mono-n-butyl phthalate is stable and resistant to hydrolysis of the second ester group. Mono-n-butyl phthalate and other metabolites are excreted in the urine mainly as glucuronide conjugates. ECOTOXICITY STUDIES: The risk to aquatic organisms associated with the present mean concentrations of DBP in surface water is low. However, in highly polluted rivers the safety margin is much smaller. Recent data show that a continuous exposure to subacute concentrations of DBP for 7 d can cause antiestrogenicity in female adult Murray rainbowfish. For DBP fed ring dove (Streptophelia risoria) eggs were examined in a 3-week experiment. Egg shell thickness was found to be decreased (10%), whereas the water permeability increased (23%). Vapor of dibutyl phthalate in light produces disturbances in carotenoid synthesis of green plants resulting in chlorophyll deficiency and in extreme cases completely chlorophyll-free leaves having a white color.
The most characteristic effect of di-n-butyl phthalate is testicular atrophy. Di-n-butyl phthalate exposure causes both the release of iron from hemoglobin and/or transferrin in the liver and spleen, and the subsequent depletion of iron in the blood and testes. The decreased amount of available iron results in a decrease in succinate dehydrogenase activity in the Sertoli cells. This results in disturbances in the energy transfer system between Sertoli cells and germ cells, which is required for the differentiation of male germ cells and their progression through the seminiferous epithelium and release as mature spermatozoa. Di-n-butyl phthalate may also exhibit weak estrogenic activity. It has been shown to exhibit toxic effects in liver mitochondria by uncoupling energy-linked processes and inhibiting succinate dehydrogenase. (L133, A105)

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Toxicity Data
LC50 (mice) = 25,000 mg/m3/2H
LD50: 3050 mg/kg (Intraperitoneal, Rat) (T13)
LD50: 720 mg/kg (Intravenous, Mouse) (T13)
LD50: 5289 mg/kg (Oral, Mouse) (T13)
LC50: 25 g/m3 over 2 hours (Inhalation, Mouse) (T13)

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Interactions
An antagonistic interaction was observed in houseflies upon simultaneous application of di-2-ethylhexyl phthalate or dibutyl phthalate with 21 organophosphates.
DBP applied to female house flies topically or by injection at a concentration of 20 ug/fly (1000 ug/g body weight) was not toxic, causing a mortality of less than 16% after 24 hr ... . Antagonistic interactions were observed when flies were treated simultaneously with DBP and various organophosphate insecticides, while synergistic interactions were observed when flies were pretreated with the phthalate 30 min before exposure to the pesticides. DBP inhibited the metabolism of organophosphate pesticides, accounting for the synergistic effects. When the phthalate and insecticides were applied simultaneously, the resulting increase in the total lipophilic pool by DBP may have resulted in an internal concentration of insecticide below the toxicity threshold.
... Adsorption of dimethyl, di-n-butyl, and di(2-ethylhexyl) phthalates using everted gut sac preparation from rat small intestine /was studied/. Monoesters were absorbed more rapidly than corresponding diesters. Esterases of the mucosal epithelium hydrolyzed the diesters to mono esters during absorption. When esterase ... inhibited by an organo-phosphate, absorption of di-n-butyl phthalate was significantly reduced.
/The objective of this study was/ to investigate the relationship between atopic allergy and depression and the role of DBP in the development of depression. BALB/c mice were randomly divided into eight groups: saline; ovalbumin (OVA)-immunized; saline+DBP (0.45 mg/kg /per/ d); saline+DBP (45 mg/kg /per/ d); DBP (0.45 mg/kg /per/d) OVA-immunized; DBP (45 mg/kgod) OVA-immunized; saline+hydrocortisone (30 mg/kg /per/d); and hydrocortisone (30 mg/kg /per/d)-exposed OVA-immunized. Behavior (e.g. open-field, tail suspension, and forced swimming tests), viscera coefficients (brain and spleen), oxidative damage [e.g. reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH)], as well as levels of IgE and IL-4, were then analyzed. In the saline and OVA groups, the degree of depression symptoms in mice increased with increasing DBP concentration. Additionally, the OVA-immunity groups were associated with more serious depressive behavior compared with the same exposure concentration in the saline group. Oxidative damage was associated with a dose-dependent increase in DBP in the different groups. IL-4 and IgE levels were associated with low-dose DBP stimulation, which changed to high-dose inhibition with increasing DBP exposure, possibly due to spleen injury seen at high DBP concentrations. Development of an atopic allergy has the potential to increase the risk of depression in mice, and it seems that DBP helps OVA to exert its effect in present model.
For more Interactions (Complete) data for DIBUTYL PHTHALATE (10 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 3050 mg/kg
LC50 Mouse inhalation 25 g/cu m/2 hr
LD50 Mouse iv 720 mg/kg
LD50 Mouse oral 5289 mg/kg.
For more Non-Human Toxicity Values (Complete) data for DIBUTYL PHTHALATE (16 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, a rickettsial disease transmitted by larvae of Leptotrombidium deliense, is of special importance to the Armed Forces personnel, due to the heightened risk to this disease during movement in mite endemic areas during exercise/war. The disease is best prevented by the use of personal protective measures including repellents. Studies were undertaken to determine the relative efficacy of repellents: diethyl toulamide (DEET), dibutyl phthalate (DBP) with an indigenously developed repellent diethyl phenyl acetamide (DEPA) against the larval trombiculid mite. The repellents were tested for persistence on impregnated cloth prior to washing, post washing and ironing by means of a specially fabricated testing kit. Acaricidal efficacy estimation was performed on the treated fabrics and topical application efficacy of repellents on mice was evaluated by a novel animal testing model. DEET and DEPA were found to provide maximum protection (repellence and acaricidal efficacy), could withstand two launderings of the impregnated uniform and also had superior efficacy on topical application (8 h). Ironing was found to significantly reduce the repellence of DEET and DBP. The findings of this study point towards the superiority of DEPA and DEET for impregnation of the uniform cloth as well as for topical application for the prevention of scrub typhus amongst the troops.

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.

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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.

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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.

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