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 in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients. A multi-center, non-interventional, observational study of excipient-kinetics in neonates. 'Dried Blood Spot' samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach. A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/mL), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CL PNA<21 days 0.57 versus CL PNA>21 days 0.88 L/hr. Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.
By the oral route, parabens are rapidly absorbed, metabolized, and excreted. The metabolic reactions and conversions in mammals vary with the chain length of the ester, the animal species, route of administration, and quantity tested. The metabolism of parabens in humans appears to be most closely related to that of dogs. The rate of metabolite excretion appears to decrease with increasing molecular weight of the ester. /Parabens/
After propyl paraben is intravenously infused into the dog, unhydrolyzed propyl paraben is found only in the brain. In liver, kidney, and muscle, it is immediately hydrolyzed to p-hydroxybenzoic acid. Six hours after oral administration of 1.0 g/kg to dogs, the peak plasma concentration of free and total propyl paraben (205 and 370 ug/cu cm) is reached. After 48 hr, all propyl paraben is eliminated.
Parabens are in widespread use as preservatives in drugs. In the late 1990s, concerns were raised about their capacity to disrupt endocrine function based on in vitro data and in vivo uterotrophic tests. Studies in juvenile male rats provided conflicting results on pospubertal sperm production. In an exploratory pharmacokinetic study, Wistar male rats received a single dose of propylparaben (PP) at 3, 10, 100, or 1000 mg/kg, orally on postnatal day (PND) 31. Plasma PP concentrations were quantifiable up 8 hr after dosing with a mean T max value of 15 min. Distribution was 4.8 L/kg, the plasma elimination half-life was 47 min, and clearance was 4.20 (L/hr)/kg at 10 mg/kg. A sulfoconjugated metabolite was detected. In the juvenile toxicology study, PP was orally administered by gavage to 20 Wistar male rats at doses of 3, 10, 100, or 1000 mg/kg/day in 1% hydroxyethylcellulose for 8 weeks starting on PND21. A first subgroup of 10 males/dose was necropsied immediately after the 8-week exposure period; a second subgroup of 10 males/dose was necropsied after a 26-week washout period. Blood samples were taken from additional satellite animals after dosing on PND21 and PND77 for toxicokinetic analysis. There was no evidence of an effect of PP on the weight of the male reproductive organs, epididymal sperm parameters, hormone levels, or histopathology. The dose of 1000 mg/kg/day was the no-observed adverse effect level, corresponding to a maximum plasma concentration of 12,030 ng/mL and exposure to 47 760 ng x hr/mL (AUC0-8 hr) at the end of the treatment.
For more Absorption, Distribution and Excretion (Complete) data for PROPYLPARABEN (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
In mice, rats, rabbits, or dogs, propyl paraben is excreted in the urine as unchanged benzoate, p-hydroxybenzoic acid, p-hydroxyhippuric acid (p-hydroxybenzoylglycine), ester glucuronides, ether glucuronides, or ether sulfates.
By the oral route, parabens are rapidly absorbed, metabolized, and excreted. The metabolic reactions and conversions in mammals vary with the chain length of the ester, the animal species, route of administration, and quantity tested. The metabolism of parabens in humans appears to be most closely related to that of dogs. The rate of metabolite excretion appears to decrease with increasing molecular weight of the ester. /Parabens/
Intravenous (IV) injections at 50 mg/kg methylparaben, ethylparaben, propylparaben, or butylparaben were administered to groups of three or more fasted dogs. Similarly, these compounds were administered orally at a dose of 1.0 g/kg. Blood and urine were analyzed at predetermined intervals. Immediately following IV injection, very little ester remained in the blood. Metabolites were detectable in the blood up to 6 hr postinjection and 24 hr postingestion. Recovery of all esters but butylparaben ranged from 58 to 94% of the administered dose. Absorption was essentially complete. ... Dogs given 50 mg/kg were then killed and the distribution of esters and metabolites to organs was determined. Pure ester was recovered only in the brain, spleen, and pancreas. High concentrations of metabolites were detected in the liver and kidneys. With in vitro assays, it was found that esterases in the liver and kidneys of the dog were extremely efficient in hydrolyzing parabens --- complete hydrolysis after 3 minutes for all parabens except butylparaben, which took 30 to 60 minutes. No accumulation of parabens was observed in the tissues of dogs given orally 1 g/kg/day methylparaben or propylparaben for 1 year. The rate of urinary excretion of esters and metabolites in these dogs increased to such an extent that after 24 hr, 96 % of the dose was excreted in the urine. This is contrasted with dogs given a single dose of paraben in which the 96 % excretion level was not attained until 48 hr.
Propyl-4-hydroxybenzoate has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-(4-propoxycarbonylphenoxy)oxane-2-carboxylic acid.

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Biological Half-Life
Propylparaben was administered orally to sexually immature rainbow trout every second day for up to 10 days in doses between 7 and 1830 mg/kg/2 days and in the water at 50 and 225 ug/L for 12 days. ... Half lives for propylparaben were 8.6 hr in liver and 1.5 hr in muscle.

Toxicity Summary
IDENTIFICATION AND USE: Propylparaben is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics. HUMAN EXPOSURE AND TOXICITY: Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure, but high concentrations of 5-15% in patch testing are needed to elicit reaction in susceptible individuals. ANIMAL STUDIES: Acute toxicity studies in animals indicate that propylparaben is relatively non-toxic by both oral and parenteral routes, although it is mildly irritating to the skin. Following chronic administration, no-observed-effect levels (NOEL) as high as 1200-4000 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) of 5500 mg/kg was reported in the rat. Propylparaben is not carcinogenic, mutagenic or clastogenic. It is not cytogenic in vitro in the absence of carboxyesterase inhibitors. Propylparaben in the diet produced cell proliferation in the forestomach of rats. Propylparaben was noncarcinogenic in a study of transplacental carcinogenesis. In one in vitro study, sperm were not viable at concentrations as low as 3 mg/mL Propylparaben. Propylparaben did affect sperm counts in vivo at all levels from 0.01% to 1.0%. ECOTOXICITY STUDIES: In a rainbow trout Oncorhynchus mykiss test system, increases in average plasma vitellogenin levels were seen at oral exposure to 33 mg propylparaben/kg/2 days; the most sensitive fish responded to 7 mg/kg. Zebrafish exposure to propylparaben at the concentrations of 0.1; 0.4 and 0.9 mg/L elicited statistically significant decline of vitellogenin production.

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Interactions
Butylated hydroxyanisole and propylparaben are phenolic preservatives commonly used in food, pharmaceutical and personal care products. Both chemicals have been subjected to extensive toxicological studies, due to the growing concern regarding their possible impacts on environmental and human health. However, the cytotoxicity and underlying mechanisms of co-exposure to these compounds have not been explored. In this study, a set of relevant cytotoxicity endpoints including cell viability and proliferation, oxidative stress, DNA damage and gene expression changes were analyzed to assess whether the antioxidant butylated hydroxyanisole could prevent the pro-oxidant effects caused by propylparaben in Vero cells. We demonstrated that binary mixtures of both chemicals induce greater cytotoxic effects than those reported after single exposureto each compound. Simultaneous treatment with butylated hydroxyanisole and propylparaben caused G0/G1 cell cycle arrest as a result of enhanced generation of oxidative stress and DNA double strand breaks. DNA microarray analysis revealed that a cross-talk between transforming growth factor beta (TGFbeta) and ataxia-telangiectasia mutated kinase (ATM) pathways regulates the response of Vero cells to the tested compounds in binary mixture. Our findings indicate that butylated hydroxyanisole potentiates the pro-oxidant effects of propylparaben in cultured mammalian cells and provide useful information for their safety assessment.
Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use -propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 uM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 uM seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 uM and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 uM. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we include mixed exposures. This study emphasizes that risk assessment of compounds should take mixture effects into account.
... Evidence that the antimicrobial effects of the parabens and sodium benzoate are additive. /Parabens/

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Non-Human Toxicity Values
LD50 Mouse oral 6.0 g/kg /From table/
LD50 Mouse oral >8000 mg/kg
LD50 Mouse ip 640 mg/kg
LD50 Mouse ip 0.4 g/kg /From table/
For more Non-Human Toxicity Values (Complete) data for PROPYLPARABEN (7 total), please visit the HSDB record 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.

Propyl-4-hydroxybenzoate appears as colorless crystals or white powder or chunky white solid. Melting point 95-98 °C. Odorless or faint aromatic odor. Low toxicity, Tasteless (numbs the tongue). pH: 6.5-7.0 (slightly acidic) in solution.
Propylparaben is the benzoate ester that is the propyl ester of 4-hydroxybenzoic acid. Preservative typically found in many water-based cosmetics, such as creams, lotions, shampoos and bath products. Also used as a food additive. It has a role as an antifungal agent and an antimicrobial agent. It is a benzoate ester, a member of phenols and a paraben. It is functionally related to a propan-1-ol and a 4-hydroxybenzoic acid.
Propylparaben is used in allergenic testing.
Propylparaben is a Standardized Chemical Allergen. The physiologic effect of propylparaben is by means of Increased Histamine Release, and Cell-mediated Immunity.
Propylparaben has been reported in Anastatica hierochuntica, Stocksia brahuica, and other organisms with data available.
Propylparaben is an antimicrobial agent, preservative, flavouring agent. Propylparaben belongs to the family of Hydroxybenzoic Acid Derivatives. These are compounds containing an hydroxybenzoic acid (or a derivative), which is a benzene ring bearing a carboxylic acid.

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Drug Indication
Propylparaben is used in allergenic testing.

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Mechanism of Action
...The mechanism of propyl paraben may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation...

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Therapeutic Uses
/EXPTL THER/ /The authors/ studied the prophylactic effect of propylparaben on alveolitis sicca dolorosa (ASD). Each of 45 patients received three tablets containing 33 mg Propylparaben or a placebo in the socket immediately after removal of a mandibular third molar. None of the patients receiving propylparaben developed ASD, whereas 24 percent of the placebo group did. The prophylatic effect of propylparaben was highly significant, and no side effects to treatment 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.

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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.

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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.

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