Isolated adult rat cardiomyocytes are shielded from ischemia-reperfusion damage by propylparaben. The effects of 15 hours of reperfusion and 45 minutes of continuous ischemia-induced cell death are considerably lessened by propylparaben (500 μM; 10 minutes) [4]. Voltage-gated sodium channels are reversibly blocked by propylparaben (250 μM, 500 μM) in a concentration- and voltage-dependent way [4]. In mature 3T3-L1 white adipocytes, propylparaben (0-1 μM; 48 hours) inhibits basal lipolysis, including insulin-stimulated glucose uptake. However, it won't alter the 2-NBDG's basic intake [5].

In eight months, female mice treated with propylparaben (7.5 mg/kg/day; oral; treated for eight months) showed dramatic changes in hormone levels, ovarian reserve, and estrous cycles. In addition, adult mice's ovarian aging was accelerated. According to studies, melatonin administration can stop the malfunction of granulosa cell steroid synthesis caused by propylparaben [6].

Absorption, Distribution and Excretion
Systemic exposure to parabens, particularly propylparaben (PPB), in newborns remains a concern. Therefore, this study determined the concentrations and kinetics of methylparaben (MPB) and PPB in the blood of newborns taking medications containing these excipients. This was a multicenter, non-interventional, observational study designed to investigate the kinetics of neonatal excipients. “Dried blood spot” samples were randomly collected concurrently with routine blood sampling, and the observations were modeled using a nonlinear mixed-effects model. A total of 841 blood MPB and PPB concentration data were collected from 181 preterm and full-term newborns for evaluation. Quantifiable MPB concentrations were detected in the blood of 99% of patients, and quantifiable PPB concentrations were detected in the blood of 49% of patients, with 55% of MPB concentrations exceeding the limit of detection (10 ng/mL) and 25% exceeding the limit of detection (10 ng/mL). Only MPB data are suitable for modeling. Oral bioavailability is affected by formulation type, and its in vivo distribution best conforms to a two-compartment model. Clearance (CL) is affected by postnatal age (PNA); the CL is 0.57 L/hr when PNA < 21 days and 0.88 L/hr when PNA > 21 days. Repeated daily administration of parabens to neonates may lead to long-term systemic exposure to the compound from the mother. Animal toxicology studies specifically targeting the neonatal period (PPB) are needed before determining the acceptable daily exposure for this age group.
Oral administration of parabens results in rapid absorption, metabolism, and excretion. 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.
After intravenous infusion of propylparaben in dogs, unhydrolyzed propylparaben is found only in brain tissue. In the liver, kidneys, and muscles, it is immediately hydrolyzed to p-hydroxybenzoic acid. In dogs, after oral administration of 1.0 g/kg propylparaben, the peak plasma concentrations of free and total propylparaben reached 205 and 370 μg/cm³, respectively, 6 hours later. All propylparaben was eliminated after 48 hours. Parabens are widely used as pharmaceutical preservatives. In the late 1990s, based on in vitro experimental data and in vivo uterine nutrition studies, concerns began to arise regarding their potential to interfere with endocrine function. Results from studies on post-pubertal spermatogenesis in juvenile male rats are controversial. In an exploratory pharmacokinetic study, Wistar male rats were given a single oral dose of propylparaben (PP) at doses of 3, 10, 100, or 1000 mg/kg on day 31 after birth (PND 31). Plasma PP concentrations were detectable within 8 hours of administration, with a mean time to peak concentration (Tmax) of 15 minutes. The volume of distribution at a dose of 10 mg/kg was 4.8 L/kg, the plasma elimination half-life was 47 minutes, and the clearance rate was 4.20 L/hr/kg. A sulfonated metabolite was detected. In juvenile toxicology studies, 20 male Wistar rats were administered PP by gavage for 8 consecutive weeks starting on day 21 (PND 21) at doses of 3, 10, 100, or 1000 mg/kg/day, dissolved in 1% hydroxyethyl cellulose solution. Ten males in each dose group of group I underwent necropsy immediately after the 8-week exposure period; ten males in each dose group of group II underwent necropsy after a 26-week washout period. Blood samples were collected from satellite animals for toxicokinetic analysis after administration on days 21 and 77 (PND21 and PND77). No effects of PP on male reproductive organ weight, epididymal sperm parameters, hormone levels, or histopathology were found. A dose of 1000 mg/kg/day represents the level at which no adverse reactions were observed, corresponding to a maximum plasma concentration of 12,030 ng/mL and an exposure of 47,760 ng·hr/mL (AUC0–8 hr) at the end of treatment. For more complete data on the absorption, distribution, and excretion of propylparaben (7 metabolites), please visit the HSDB record page. Metabolites/Metabolites In mice, rats, rabbits, or dogs, propylparaben is excreted in the urine as unmetabolized benzoate, parahydroxybenzoic acid, parahydroxyhippuric acid (parahydroxybenzoylglycine), ester glucuronide, ether glucuronide, or ether sulfate. Following oral administration, parabens are rapidly absorbed, metabolized, and excreted. In mammals, the metabolic response and transformation of parabens vary with 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 excretion rate of metabolites appears to decrease with increasing ester molecular weight. /parabens/
Three or more fasting dogs were administered intravenous injections of methylparaben, ethylparaben, propylparaben, or butylparaben at doses of 50 mg/kg. These compounds were also administered orally at doses of 1.0 g/kg. Blood and urine were analyzed at predetermined time intervals. Very few esters remained in the blood after intravenous injection. 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 dogs given the 50 mg/kg dose were subsequently sacrificed, and the distribution of esters and their metabolites in various organs was determined. Pure esters were detected 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 liver and kidneys of dogs were highly efficient at hydrolyzing parabens (such as butylparaben)—all parabens were completely hydrolyzed within 3 minutes, except for butylparaben, which required 30 to 60 minutes. No accumulation of parabens was observed in the tissues of dogs that received 1 g/kg of methylparaben or propylparaben orally daily for one year. The excretion rate of esters and their metabolites in the urine of these dogs was significantly increased; 96% of the dose was excreted in the urine after 24 hours. This contrasts with dogs that received a single dose of parabens, which only reached 96% excretion after 48 hours.
The known human metabolites of propyl 4-hydroxybenzoate include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-(4-propoxycarbonylphenoxy)oxacyclohexane-2-carboxylic acid.
Biological half-life

In immature rainbow trout, propyl 4-hydroxybenzoate was administered orally every other day for 10 days, at doses ranging from 7 to 1830 mg/kg/2 days; simultaneously, it was administered in water at concentrations of 50 and 225 μg/L for 12 days. …The half-life of propyl 4-hydroxybenzoate in the liver is 8.6 hours, and in muscle it is 1.5 hours.

Toxicity Summary
Identification and Uses: Propylparaben is a stable, non-volatile compound used as an antimicrobial preservative in food, pharmaceuticals, and cosmetics. Human Exposure and Toxicity: Sensitization can occur when drugs containing parabens are applied to damaged or broken skin. Parabens are associated with many cases of contact sensitization via skin contact, but high concentrations of 5-15% are required in patch tests to induce a reaction in susceptible individuals. Animal Studies: Acute toxicity studies in animals have shown that propylparaben has relatively low toxicity when administered orally and parenterally, but exhibits mild skin irritation. After prolonged administration, the reported no-observed-effect level (NOEL) is as high as 1200-4000 mg/kg, and the reported no-observed-adverse-effect level (NOAEL) in rats is 5500 mg/kg. Propylparaben is not carcinogenic, mutagenic, or chromosomally disruptive. In in vitro studies, it is not cytopathic in the absence of carboxylesterase inhibitors. Dietary propylparaben can cause proliferation of forestomach cells in rats. In a transplacental carcinogenicity study, propylparaben was not carcinogenic. In an in vitro study, concentrations as low as 3 mg/mL of propylparaben caused sperm motility loss. In in vivo experiments, propylparaben affected sperm count at all concentration levels from 0.01% to 1.0%. Ecotoxicity studies: In rainbow trout (Oncorhynchus mykiss) assay systems, oral exposure to 33 mg/kg/2 days of propylparaben resulted in increased mean plasma vitellogenin levels; the most sensitive fish responded to a dose of 7 mg/kg. In zebrafish, exposure to 0.1 mg/kg of propylparaben, concentrations of 0.4 and 0.9 mg/L caused significant decreases in vitellogenin production. Interactions Butylated hydroxyanisole (BHA) and propylparaben are commonly used phenolic preservatives in food, pharmaceuticals, and personal care products. Due to increasing concerns about their potential environmental and human health impacts, both chemicals have undergone extensive toxicological studies. However, the cytotoxicity and underlying mechanisms of co-exposure to these two compounds have not been explored. In this study, we analyzed a range of relevant cytotoxic endpoints, including cell viability and proliferation, oxidative stress, DNA damage, and changes in gene expression, to assess whether the antioxidant BHA could prevent the pro-oxidative effects induced by propylparaben in Vero cells. We demonstrated that the binary mixture of these two chemicals produced stronger cytotoxic effects than exposure to each compound alone. Simultaneous treatment of cells with BHA and propylparaben resulted in G0/G1 phase cell cycle arrest due to increased oxidative stress and DNA double-strand breaks. DNA microarray analysis revealed that the interaction between transforming growth factor β (TGFβ) and ataxia-telangiectasia mutant kinase (ATM) pathways modulates the response of Vero cells to the test compounds in a binary mixture. Our results indicate that butylated hydroxyanisole enhances the pro-oxidative activity of propylparaben in cultured mammalian cells and provides useful information for assessing its safety. Endocrine disruptors can interfere with endocrine organs or hormone systems, leading to tumors, birth defects, and developmental disorders in humans. While the estrogen-like activity of these compounds has been extensively studied, their potential role in regulating glucocorticoid receptors is 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 responsible for regulating 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 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 were identified as having 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 activities were increased by 1.25 to 1.51 times at 1 μM concentration and by 1.23 to 1.44 times 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 at 10 nM concentrations did not show glucocorticoid-like activity, while BP showed a 1.44-fold increase in 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. ...There is evidence that the antibacterial effects of parabens and sodium benzoate have an additive effect. /parabens/

---

Non-human toxicity values
Oral LD50 in mice: 6.0 g/kg /Table/
Oral LD50 in mice: >8000 mg/kg
Intraperitoneal LD50 in mice: 640 mg/kg
Intraperitoneal LD50 in mice: 0.4 g/kg /Table/
For more complete non-human toxicity data for propylparabens (7 types in total), please visit the HSDB records page.

[1]. Gal A, et, al. Propylparaben inhibits mouse cultured antral follicle growth, alters steroidogenesis, and upregulates levels of cell-cycle and apoptosis regulators. Reprod Toxicol. 2019 Oct;89:100-106.
[2]. Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products. Int J Toxicol. 2008;27 Suppl 4:1-82.
[3]. S Oishi, et al. Effects of propyl paraben on the male reproductive system. Food Chem Toxicol. 2002 Dec;40(12):1807-13.

4-Hydroxybenzoate is a colorless crystal, white powder, or lumpy white solid. Melting point: 95-98℃. Odorless or slightly aromatic. Low toxicity, odorless (can numb the tongue). Solution pH: 6.5-7.0 (weakly acidic).
Propylparaben is a propyl ester derivative of 4-hydroxybenzoic acid. It is a common preservative widely used in many water-based cosmetics, such as creams, lotions, shampoos, and bath products. It can also be used as a food additive. It has antifungal and antibacterial properties. It is a benzoic acid ester, belonging to the phenolic and para-hydroxybenzoic acid ester classes. Its structure is related to propan-1-ol and 4-hydroxybenzoic acid.
Propylparaben is used in allergen testing.
Propylparaben is a standardized chemical allergen. The physiological effects of propylparaben are achieved by increasing histamine release and cell-mediated immunity.
According to reports, propylparaben has been found in organisms with relevant data, such as Anastatica hierochuntica and Stocksia brahuica.
Propylparaben is an antibacterial agent, preservative, and flavoring agent. It belongs to the family of hydroxybenzoic acid derivatives. These compounds contain hydroxybenzoic acid (or its derivatives), which is a benzene ring with a carboxylic acid group.
Pharmacological Indications

Propylparaben is used for allergen testing.
Mechanism of Action

...The mechanism of action of propylparaben may be related to mitochondrial dysfunction, which depends on the induction of membrane permeability switching, accompanied by mitochondrial depolarization and cellular ATP depletion caused by uncoupling through oxidative phosphorylation...
Therapeutic Uses

/Experimental Treatment/ /Authors/ Investigated the preventive effect of propylparaben on dry alveolar dermatitis (ASD). Forty-five patients had three tablets containing either 33 mg of propylparaben or a placebo placed in their alveolar sockets immediately after extraction of their mandibular third molars. None of the patients taking propylparaben developed autism spectrum disorder (ASD), compared to 24% in the placebo group. The preventative effect of propylparaben was highly significant, and no treatment side effects were reported.

C10H12O3

180.2

180.078

94-13-3

Propylparaben-d7;1246820-92-7;Propylparaben-d4;1219802-67-1;Propylparaben sodium;35285-69-9

7175

White to off-white solid powder

1.1±0.1 g/cm3

294.3±13.0 °C at 760 mmHg

95-98 °C(lit.)

124.6±12.6 °C

0.0±0.6 mmHg at 25°C

1.532

2.93

1

3

4

13

160

0

QELSKZZBTMNZEB-UHFFFAOYSA-N

InChI=1S/C10H12O3/c1-2-7-13-10(12)8-3-5-9(11)6-4-8/h3-6,11H,2,7H2,1H3

propyl 4-hydroxybenzoate

NSC-23515; NSC 23515; Propylparaben

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 : ~125 mg/mL (~693.67 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (11.54 mM) (saturation unknown) in 10% DMSO + 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 20.8 mg/mL clear DMSO 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: ≥ 2.08 mg/mL (11.54 mM) (saturation unknown) in 10% DMSO + 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 20.8 mg/mL clear DMSO 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: ≥ 2.08 mg/mL (11.54 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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