In pigs, butylparaben (0-500 μM, 44 hours) inhibits the rates of fertilization, cleavage, and blastocyst formation [2]. In pig oocytes, butylparaben causes DNA damage, cell sealing, and autophagy [2].

For 13 weeks, butylparaben (0–50 mg/kg/day) administered subcutaneously did not cause systemic toxicity [1].

Absorption, Distribution and Excretion
Following oral administration, parabens are rapidly absorbed, metabolized, and excreted. Metabolic responses and transformations in mammals vary depending on ester chain length, animal species, route of administration, and test dose. The metabolism of parabens in humans appears to be most similar to that in dogs. The rate of metabolite excretion appears to decrease with increasing ester molecular weight. /4-Hydroxybenzoate (paraben)/ Following intravenous infusion of butylparaben in dogs, unhydrolyzed butylparaben was detected in the brain, spleen, and pancreas. In the liver, kidneys, and muscle, it is immediately hydrolyzed to parabens. Peak plasma concentrations of free and total butylparaben were reached 6 hours after oral administration of 1.0 g/kg in dogs (15 and 141 μg/cm³, respectively). Butylparaben was eliminated after 48 hours. This study investigated the permeation of methyl, ethyl, propyl, and butyl parabens through isolated guinea pig dorsal skin and observed the effects of permeation enhancers (levomenthine plus ethanol and N-dodecyl-2-pyrrolidone). The permeation coefficient of parabens was correlated with the n-octanol/water partition coefficient. Adding 1% levomenthine to a 15% ethanol solution increased the permeation coefficient of methyl parabens by approximately 16-fold, while the same enhancer reduced the permeation coefficient of butyl parabens to about one-fifth of the control group. A similar, but weaker, trend was observed with the 15% ethanol solution itself. A 0.025% N-dodecyl-2-pyrrolidone suspension increased the permeation coefficient of methyl parabens by approximately 7-fold, but had no significant effect on the permeation coefficient of butyl parabens. Therefore, in the presence of this compound, the dependence of the permeation coefficient of parabens on the n-octanol/water partition coefficient almost disappeared. A spin-labeling study using stratum corneum liposomes showed that these permeation enhancers increase the fluidity of the lipid bilayer, corresponding to their effect on enhancing the skin permeation of methylparaben. Therefore, perturbation of the stratum corneum lipid layer structure appears to be associated with its enhanced absorption of hydrophilic parabens. Three or more fasting dogs were administered intravenous doses of methylparaben, ethylparaben, propylparaben, or butylparaben. These compounds were also administered orally at a dose of 1.0 g/kg. Blood and urine were analyzed at predetermined time intervals. Very little ester residue remained in the blood after intravenous administration. Metabolites were detectable in the blood within 6 hours after injection and within 24 hours after oral administration. Except for butylparaben, the recoveries of all esters ranged from 58% to 94% of the administered dose. Absorption was substantially complete. The recovery rate of butylparaben after oral administration was 40%, and after intravenous administration, it was 48%. The authors attribute this to the low hydrolytic efficiency of butylparaben. Dogs given a 50 mg/kg dose were subsequently euthanized, and the distribution of esters and their metabolites in various organs was determined. Pure esters were recovered only in the brain, spleen, and pancreas. High concentrations of metabolites were detected in the liver and kidneys. In vitro studies showed that esterases in the canine liver and kidneys have extremely high hydrolytic efficiency for parabens—all parabens except butylparaben were completely hydrolyzed within 3 minutes, while butylparaben required 30 to 60 minutes. Dogs that received 1 g/kg methylparaben or propylparaben orally daily for one year did not show any accumulation of parabens in their tissues. These dogs exhibited a significantly increased urinary excretion rate of esters and their metabolites; after 24 hours, 96% of the dose was excreted in the urine. In contrast, dogs given a single dose of parabens only achieved a 96% excretion rate after 48 hours. When 10% hydrophilic ointment of methylparaben or propylparaben was applied to the skin of rabbits for 48 hours, no esters or their metabolites were detected in the kidneys. For more complete data on the absorption, distribution, and excretion of butylparaben (9 in total), please visit the HSDB records page. Metabolites/Metabolites In mice, rats, rabbits, or dogs, butylparaben is excreted in the urine as unmetabolized benzoate, parahydroxybenzoic acid, parahydroxyhippuric acid (parahydroxybenzoylglycine), ester glucuronide, ether glucuronide, or ether sulfate. Following oral administration, paraben esters are rapidly absorbed, metabolized, and excreted. Metabolic responses and transformations in mammals vary depending on ester chain length, animal species, route of administration, and test dose. The metabolism of parabens in humans appears to be most similar to that in dogs. The rate of metabolite excretion appears to decrease with increasing ester molecular weight. /4-Hydroxybenzoate (p-hydroxybenzoate)/
This paper describes the permeation and metabolism of butyl p-hydroxybenzoate in living full-thickness human skin. …After 24 hours, a total of 21% of the radiolabeled material permeated into the recipient fluid. …In this full-thickness skin study, the major metabolite hydroxybenzoic acid was detected in the recipient fluid, the content of butyl p-hydroxybenzoate was very low, and ethyl p-hydroxybenzoate was not detected. …The above study was repeated to re-examine the permeation and metabolism of 0.4% butyl p-hydroxybenzoate in an oil/water emulsion in the same living full-thickness human skin…A limited dose (10 L/cm²) of the emulsion was applied to the skin surface and kept in contact for 24 hours without occlusion. (14)C-butyl p-hydroxybenzoate (labeled on the carbon ring) was measured in the recipient fluid. After 24 hours, an average of 14.9% (±3.73%) of the radiolabeled material permeated into the full-thickness human skin. The major metabolite p-hydroxybenzoic acid (p-hydroxybenzoic acid) was detected in the recipient fluid in all 10 replicates (skin samples from two individuals) (mean concentration 15.2% ± 5.23%), but the parent butylparaben (butylparaben) was almost undetectable in only 5 of the 10 replicates (mean concentration 0.225% ± 0.063%). The authors interpret these results as confirmation that butylparaben is almost completely metabolized to p-hydroxybenzoic acid in human skin via first-pass metabolism. A study on the in vitro skin penetration and metabolism of methylparaben and butylparaben in rat and human skin has been conducted. For each p-hydroxybenzoic acid ester, water-in-oil emulsions containing radiolabeled (C-labeled on the carbon-14 ring) and non-radiolabeled p-hydroxybenzoic acid esters were prepared at target concentrations of 0.8% for methylparaben and 0.4% for butylparaben. Skin samples (10 replicates from rat skin and 13 replicates from human skin) were placed in a flow-through diffusion cell. The test emulsion was applied uniformly to the skin at a flow rate of 10 L/cm² in a single application without occlusion. Receptor 2 liquid samples from the same skin were mixed with reference standards, acetonitrile was added, and the mixture was filtered. Methylparaben, butylparaben, and hydroxybenzoic acid were then analyzed using liquid chromatography-mass spectrometry (LC-MS). …For butylparaben, 52.3% was metabolized to hydroxybenzoic acid, with only 5.5% existing as unmetabolized butylparaben. In human skin, the metabolism of butylparaben differs…Of butylparaben, 32.8% exists as hydroxybenzoic acid, and 49.7% exists as unmetabolized butylparaben.
For more complete metabolite/metabolite data on butylparaben (9 metabolites in total), please visit the HSDB record page.
It is known that the human metabolites of butyl-4-hydroxybenzoic acid include (2S,3S,4S,5R)-6-(4-butoxycarbonylphenoxy)-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.

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Biological half-life
Butyl-p-hydroxybenzoic acid esters are rapidly cleared from hepatocytes in rats (t(1/2) = 3-4 min) and humans (t(1/2) = 20-30 min).

Toxicity Summary
Identification and Uses: Human Exposure and Toxicity: Butylparaben is irritating to human skin. Volunteer studies failed to identify any sensitization, but butylparaben has been shown to cause sensitization in patients with dermatitis. Animal Studies: Mice treated with the ester showed low acute oral toxicity, while the sodium salt showed moderate toxicity. In mice, butylparaben affected the spleen and thymus, as well as the liver. Dietary butylparaben caused proliferation of forestomach cells in rats, but no carcinogenicity was found in chronic feeding studies in mice. No mutagenicity was found in the Ames bacterial assay. In an in vitro study, concentrations as low as 1 mg/mL of butylparaben caused sperm inactivation. Oral administration of 1% butylparaben to rats has been reported to reduce epididymal and seminal vesicle weight; daily exposure of female rats to 100 mg/kg of butylparaben has been reported to decrease sperm count and motility in their F1 generation. Subcutaneous injection of parabens at 100 or 200 mg/kg/day in female mice resulted in decreased sperm count and motility in their F1 generation offspring, but no abnormalities were observed in the reproductive organs. Parabens can bind to estrogen receptors in isolated rat uterus, but their affinity is several orders of magnitude lower than that of natural estradiol. Ecotoxicity studies: Consistent with hydrophobic predictions, parabens with shorter alkyl chains exhibited lower aquatic toxicity to fish, water fleas, and algae than those with longer alkyl chains. Plasma vitellogenin concentrations in male killifish increased after 14 days of treatment with 200 μg/L and 100 μg/L n-butylparaben and isobutylparaben. In rainbow trout (Oncorhynchus mykiss), an average increase in plasma vitellogenin levels was observed after oral administration of 9 mg/kg butylparaben for two consecutive days. In another experiment, 10 mg/kg body weight of butylparaben exhibited estrogen-like effects in rainbow trout.

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Interactions
This study used the MDA-kb2 cell line to evaluate the individual and combined (binary) (anti)androgenic effects of butylparaben (BuPB), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and propyl gallate (PG), both individually and in combination (binary mixtures). Exposure of these cells to androgen receptor agonists induced the expression of a reporter gene (encoding luciferase), and the activity of the reporter protein was monitored by measuring luminescence intensity. To assess antiandrogenic effects, individual test compounds or binary mixtures were tested in the presence of a fixed concentration of a potent androgen receptor agonist (1000 pM 5α-dihydrotestosterone; DHT). Cell viability was assessed using a resazurite-based cell viability assay. This is the first report in the literature of the (anti)androgenic activity of PG. Neither single compounds nor mixtures showed androgenic activity in any of the compounds or binary combinations tested. BuPB, BHA, and BHT exhibited weak antiandrogenic activity in the presence of DHT, which was also confirmed in the evaluation of binary mixtures (BuPB+BHA, BuPB+BHT, and BHA+BHT). In addition to in vitro testing of the binary combinations, the accuracy of two mathematical models (dose-additive and reaction-additive models) in predicting the antiandrogenic effects of the selected binary mixtures was evaluated. The dose-additive model ensured a good correlation between experimental and predicted data. However, since compound PG showed no effect in individual tests, it was impossible to estimate the effects of mixtures containing PG. Parabens and phthalates are commercial chemicals widely used in industrial and consumer product manufacturing and are also frequently present as contaminants in biological fluids. We evaluated the effects of di(2-ethylhexyl) phthalate (DEHP) (concentration range 10⁻⁹ to 10⁻⁷ mol [1-100 nm; 0.39-39 ng/mL]) and butylparaben (BP) (concentration range 10⁻⁸ to 10⁻⁵ mol [10 nm-10 μm; 1.9 ng·mol/L to 1.9 μg/mL]), alone and in combination, on isolated mouse preantral follicles and human granulosa cell (hGC) cultures to investigate their direct effects on follicle growth and ovarian steroid production. Our results indicate that dioctyl phthalate (DEHP) and butylparaben (BP) attenuate estradiol secretion in follicle cultures, but this only occurs when both are present simultaneously. DEHP reduced progesterone concentrations in human follicular granulosa cell (hGC) cultures, an effect attenuated when BP and DEHP were added simultaneously. Despite altered steroid production, no effects on follicular development or survival were observed in the culture system. We propose that BP and DEHP reduce estradiol production in a synergistic effect, with BP blocking the effect of DEHP on hGCs in later follicular development, leading to reduced progesterone secretion. Our combined findings suggest that dioctyl phthalate (DEHP) and phenol (BP) adversely affect steroid production from the preantral stage, and that the effects of these chemicals are stage-dependent and altered by co-exposure. To assess the estrogenic activity of several chemicals (e.g., 17β-estradiol (E2), nonylphenol, bisphenol A, butylparaben, and combinations thereof), the authors used recombinant yeast containing human estrogen receptors [Saccharomyces cerevisiae ER+LYS 8127]. …In recombinant yeast experiments, E2 showed the highest activity, followed by nonylphenol, bisphenol A, and butylparaben. Certain concentrations of 17β-estradiol (a potent estrogen) combined with either bisphenol A or butylparaben (a weak estrogen) exhibited additive estrogenic effects. Furthermore, certain concentrations of nonylphenol ether and butylparaben, as well as combinations of butylparaben and bisphenol A, showed additive estrogenic activity. Therefore, the estrogenic activity of the two chemical combinations is additive, not synergistic.
Exposure to endocrine disruptors (EDCs) during development may have negative effects on adult life. This study investigated the effects of perinatal exposure to mixtures of human-related EDCs on the female reproductive system. Female rats were exposed to a mixture of phthalates, pesticides, UV filters, bisphenol A, butylparaben, and acetaminophen. These compounds were tested simultaneously (total mixture) or grouped by their anti-androgen (AAmix) or estrogen (Emix) potential. Acetaminophen was tested alone. In prepubertal rats, the number of primordial follicles was significantly reduced in the AAmix and PM groups, and plasma prolactin levels were decreased in the AAmix group. In one-year-old animals, the incidence of irregular estrous cycles was higher after Totalmix exposure, and ovarian weight was reduced in the Totalmix, AAmix, and PM groups. These findings are similar to premature ovarian failure in humans and raise concerns about the potential impact of endocrine disruptor mixtures on female reproductive function. Endocrine disruptors can interfere with endocrine organs or hormone systems and lead to tumors, birth defects, and developmental disorders in humans. The estrogen-like activity of these compounds has been extensively studied, but the mechanisms by which they may regulate glucocorticoid receptors are poorly understood. Steroidal (synthetic and natural) and nonsteroidal endocrine-active compounds often exist in the human environment in complex mixtures. Identifying the types of molecules that can regulate glucocorticoid receptors is crucial for a comprehensive assessment of their risks. We used the MDA-kb2 cell line, expressing endogenous glucocorticoid receptors and stably transfected with a luciferase reporter gene construct, to quantitatively analyze the glucocorticoid-like activities of four compounds commonly found in everyday consumer goods: propylparaben (PP), butylparaben (BP), dioctyl phthalate (DEHP), and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 μM and 10 nM) and compared their glucocorticoid-like activities. At 1 μM, all seven mixtures except DEHP+TM, BP+TM, DEHP+PP+TM, and BP+PP+TM exhibited glucocorticoid-like activity. At 10 nM, only three mixtures showed glucocorticoid-regulating activity: DEHP+PP, BP+PP, and DEHP+BP+PP+TM. Compared to the solvent control group, the identified glucocorticoid-like activity was 1.25 to 1.51 times higher at 1 μM concentration and 1.23 to 1.44 times higher at 10 nM concentration. Individually, BP, PP, and DEHP showed glucocorticoid-like activities at 1 μM concentration that were 1.60, 1.57, and 1.50 times higher than the solvent control group, respectively. On the other hand, PP and DEHP showed no glucocorticoid-like activity at 10 nM concentration, while BP showed 1.44 times the activity. The notion that individual glucocorticoid-like compounds are harmless because they are present in low concentrations and ineffective in the human body may not hold true when considering mixed exposures. This study emphasizes that the risk assessment of compounds should consider mixed effects.

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Non-human toxicity values
Oral LD50 in mice (dd strain): 13200 mg/kg
Oral LD50 in mice: 5.0 g/kg
Intraperitoneal LD50 in mice: 230 mg/kg

[1]. Thirteen-week subcutaneous repeated dose toxicity study of butylparaben and its toxicokinetics in rats. Arch Toxicol. 2021 Jun;95(6):2037-2050.

[2]. Butylparaben Is Toxic to Porcine Oocyte Maturation and Subsequent Embryonic Development Following In Vitro Fertilization. Int J Mol Sci. 2020 May 24;21(10):3692.

N-butyl-p-hydroxybenzoate is an odorless white crystal or crystalline powder. It is tasteless but can numb the tongue. Its aqueous solution is weakly acidic to litmus paper. (NTP, 1992)
Butylparaben is an organic molecular entity.
Butylparaben is a standardized chemical allergen. The physiological effects of butylparaben are achieved through increased histamine release and cell-mediated immunity.
Butylparaben has been reported in both strychnos cathayensis and papaya, and relevant data are available.
Butylparaben is a preservative and flavoring agent. Butylparaben has been shown to have antibacterial properties. Butylparaben belongs to the hydroxybenzoic acid derivative family. These compounds contain hydroxybenzoic acid (or its derivatives), which refers to a benzene ring with a carboxylic acid group. (A3205).
See also: Butylparaben; Ethylparaben; Methylparaben (ingredient).

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Therapeutic Use
It is used in combination with other parabens as a pharyngeal disinfectant.

C11H14O3

194.2271

194.094

94-26-8

Butylparaben-d4;1219798-67-0;Butylparaben-13C6;1416711-53-9;Butylparaben sodium;36457-20-2;Butylparaben-d9;1216904-65-2

7184

White to off-white solid powder

1.1±0.1 g/cm3

309.2±15.0 °C at 760 mmHg

67-70 °C(lit.)

129.2±13.2 °C

0.0±0.7 mmHg at 25°C

1.526

3.46

1

3

5

14

171

0

QFOHBWFCKVYLES-UHFFFAOYSA-N

InChI=1S/C11H14O3/c1-2-3-8-14-11(13)9-4-6-10(12)7-5-9/h4-7,12H,2-3,8H2,1H3

butyl 4-hydroxybenzoate

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)

DMSO : ≥ 2.0 mg/mL (~10.30 mM)

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.)