The primary target of Ethylparaben is the microbial cell membrane. As a preservative, it disrupts the cell membrane of bacteria and fungi, leading to cell lysis and death. The exact molecular mechanism involves the inhibition of microbial growth by interfering with membrane transport and enzyme function. Ethylparaben also has weak estrogenic activity, acting as an endocrine disruptor.

Ethyl paraben (0-20 mg/mL) demonstrates antimicrobial and antifungal properties against several pathogens [1].
In vitro, ethylparaben has been shown to have antimicrobial activity against a range of bacteria and fungi. It inhibits the growth of various microorganisms in culture. The compound's estrogenic activity has been confirmed in cell-based assays, where it activates estrogen receptor-mediated gene expression.

Ethyl paraben (0–40 mg/kg, intragastrically) raises the levels of estrogen hormone response genes and the estrogen weight of SD estrogen [1].
In vivo, ethylparaben is used as a preservative in cosmetics, pharmaceuticals, and food products. It is absorbed through the skin and gastrointestinal tract. The compound is metabolized and excreted in the urine. Its estrogenic activity has raised concerns about its potential endocrine-disrupting effects.

In vitro enzyme or receptor binding (non-cell) assays for ethylparaben involve studying its binding to the estrogen receptor. Radioligand binding assays are performed using purified estrogen receptor or cell lysates expressing the receptor. The compound is incubated with a radiolabeled ligand, and the displacement of the ligand is measured to determine the affinity.

In vitro cell-based assays for ethylparaben are performed using estrogen-responsive cell lines, such as MCF-7 breast cancer cells. Cells are treated with the compound, and cell proliferation and estrogen-responsive gene expression are measured. The compound's antimicrobial activity is assessed using standard microbial susceptibility testing methods.

In vivo animal experiments for ethylparaben are conducted using rodent models to study its toxicological effects, including reproductive toxicity and endocrine disruption. The compound is administered orally or dermally, and its effects on reproductive organs, hormone levels, and other parameters are assessed.

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 excretion rate of metabolites appears to decrease with increasing ester molecular weight. /4-Hydroxybenzoate (parabens)/ …Deposition of parabens in dogs. Except for butyl ester, which had a recovery rate of 40%, the urinary recovery rates of other esters ranged from 50% to 95%. /It/ …It is concluded that esters are well absorbed, and ester bond hydrolysis and metabolic conjugation are the main elimination pathways. Similar metabolic mechanisms…in humans. Parabens
This study investigated the permeation of methylparaben, ethylparaben, propylparaben, and butylparaben in untreated and lipid-depleted isolated guinea pig dorsal skin, and the effects of three permeation enhancers—N-dodecyl-2-pyrrolidone (laurylpyrrolidone), ethanol, and a mixture of menthol and ethanol—on these parabens. The relationship between the permeability of these parabens and their octanol/water partition coefficients was also investigated, as well as the effects of the permeation enhancers on the fluidity of liposomes containing stratum corneum lipids. The results showed that in untreated guinea pig skin, the permeability of these parabens was positively correlated with their octanol/water partition coefficients. In lipid-depleted guinea pig skin, the permeability of parabens increased, and this was not correlated with their octanol/water partition coefficients. The effects of the permeation enhancers on paraben permeation varied. The osmosis enhancer increased the fluidity of the liposome lipid bilayer. Following intravenous infusion of ethylparaben in dogs, unhydrolyzed ethylparaben was found only in brain tissue. In the liver, kidneys, and muscle, it was immediately hydrolyzed to para-hydroxybenzoic acid. Six hours after oral administration of 1.0 g/kg ethylparaben to dogs, the peak plasma concentrations of free and total ethylparaben reached 427 and 648 μg/cm³, respectively. After 48 hours, all ethylparaben was completely cleared. Metabolism/Metabolites: Para-hydroxybenzoic acid is produced in pigs and Aspergillus. /Excerpt from Table/ Para-hydroxybenzoic acid esters are well absorbed in dogs, with ester bond hydrolysis and metabolic conjugation being the main clearance pathways. Similar metabolic patterns have been observed in humans. Parabens
Orally administered 14C-labeled ethyl paraben contains two major metabolites in the urine of cats: p-hydroxyhippuric acid and free p-hydroxybenzoic acid.
In mice, rats, rabbits, pigs, or dogs, ethyl paraben is excreted in urine as unmodified benzoate, p-hydroxybenzoic acid, p-hydroxyhippuric acid (p-hydroxybenzoylglycine), ester glucuronide, ether glucuronide, or ether sulfate.
For more complete metabolite/metabolite data on ethyl paraben (7 metabolites in total), please visit the HSDB record page.
Known human metabolites of ethyl paraben include (2S,3S,4S,5R)-6-(4-ethoxycarbonylphenoxy)-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.
Pharmacokinetic (PK) properties of ethylparaben indicate that it is absorbed through the skin and gastrointestinal tract. The compound has a molecular weight of 166.17 and a molecular formula of C9H10O3. It is a white crystalline powder. It is metabolized by esterases to para-hydroxybenzoic acid, which is excreted in the urine.

Toxicity Summary
Identification and Uses: Ethyl parabens form colorless small crystals or a white powder. Ethyl parabens inhibits the growth of fungi and bacteria and is used as a preservative in pharmaceuticals, adhesives, and various cosmetic preparations. Human Exposure and Toxicity: Ethyl parabens are irritating to human skin. One human study did not find any sensitizing effects. Parabens are a class of general substances and rarely cause sensitization when applied to intact human skin. Application to damaged skin is a more common cause of sensitization. Oral administration of a mixture of methylparaben, ethylparaben, and propylparaben has been shown to exacerbate pre-existing skin problems. Animal Studies: Ethyl parabens are irritating to the eyes of rabbits. In laboratory animals, acute oral toxicity of ethylparaben is low. Limited long-term studies in rats have shown that ethylparaben has low toxicity and no carcinogenic activity was found. Dietary addition of ethylparaben can lead to proliferation of forestomach cells in rats. Limited Ames bacterial assays did not reveal mutagenicity. Ethylparaben did increase chromosomal aberrations in Chinese hamster ovarian cells, but similar effects were not observed in rats treated with ethylparaben. Oral administration of ethylparaben to pregnant female rats resulted in fetal toxicity at doses reaching maternal toxicity levels. Ethylparaben was not teratogenic in rats. An in vitro study showed that ethylparaben at concentrations as low as 8 mg/mL caused loss of sperm motility; however, an in vivo study showed that adding 0.1% or 1.0% ethylparaben to the diet of mice did not produce sperm toxicity.

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Interactions
The biological metabolic pathway of ethylparaben when co-administered with salicylic acid differs from that previously reported when ethylparaben was used alone.
The excretion of the hydrolysis product of ethylparaben—unconjugated paraben—is increased, while the excretion of the glycine conjugates of paraben—para-hydroxyhippuric acid and its ester glucuronide—is decreased. Blood concentration patterns differ significantly from those observed with ethylparaben alone, particularly with delayed elimination of all metabolites. Pharmacokinetic analysis of blood concentration data also revealed the effect of salicylic acid on the biometabolism of ethylparaben.

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Non-human toxicity values
LD50 Rat (female) oral 4.30 g/kg
LD50 Rat oral 11.0 g/kg
LD50 Guinea pig oral 2.0 g/kg /from table/
LD50 Rabbit oral 5.0 g/kg /from table/
For more non-human toxicity values (complete data) for ethylparaben (9 items in total), please visit the HSDB record page.
Toxicology (toxicology) data for ethylparaben indicate that it is generally regarded as safe for use as a preservative at low concentrations. However, its estrogenic activity has raised concerns about potential endocrine-disrupting effects. It may cause skin irritation and allergic reactions in some individuals. The compound should be used at concentrations within regulatory limits.

[1]. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats. Sci Rep. 2016 Apr 28;6:25173.

[2]. Identification of ethylparaben as the antimicrobial substance produced by Brevibacillus brevis FJAT-0809-GLX. Microbiol Res. 2015 Mar;172:48-56.

Ethyl paraben is an ethyl ester formed by the condensation of the carboxyl group of 4-hydroxybenzoic acid with ethanol. It functions as an antibacterial food preservative, antifungal agent, plant metabolite, and phytoestrogen. It is both a preservative and an ethyl ester. Ethyl paraben is a standardized chemical allergen. Its physiological effects are achieved through increased histamine release and cell-mediated immunity. Ethyl paraben has been reported in Aeschynanthus bracteatus, Inula salsoloides, and other organisms with relevant data. Ethyl paraben is present in alcoholic beverages. It is an antibacterial and preservative. It is found in red wine, white wine, and sake. Ethyl paraben 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. Ethyl 4-hydroxybenzoic acid is a metabolite found or produced in Saccharomyces cerevisiae.
Other information: Ethylparaben is a preservative used in cosmetics, pharmaceuticals, and food products. It is also known as Ethyl parahydroxybenzoate and E214. The compound has antimicrobial and preservative properties. Its CAS number is 120-47-8.

C9H10O3

166.18

166.062

120-47-8

Ethylparaben-d4;1219795-53-5

8434

White to off-white solid powder

1.2±0.1 g/cm3

297.5±0.0 °C at 760 mmHg

114-117 °C(lit.)

120.3±12.6 °C

0.0±0.6 mmHg at 25°C

1.539

2.4

1

3

3

12

148

0

NUVBSKCKDOMJSU-UHFFFAOYSA-N

InChI=1S/C9H10O3/c1-2-12-9(11)7-3-5-8(10)6-4-7/h3-6,10H,2H2,1H3

ethyl 4-hydroxybenzoate

NSC23514; NSC 23514; Ethylparaben

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 : ~100 mg/mL (~601.79 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (15.04 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 25.0 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: ≥ 2.5 mg/mL (15.04 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 25.0 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: ≥ 2.5 mg/mL (15.04 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 25.0 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.)