Methyl p-hydroxybenzoate (Methylparaben) is a 4-hydroxybenzoate ester of p-hydroxybenzoic acid.

The name defines the structure of the molecule

• "Methyl" indicates the presence of a methyl group, which is an alkyl group with the formula CH₃.
• "p-hydroxy" indicates the presence of a hydroxy group (OH) in the para position relative to the benzoate functional group on the benzene structure.
• "Benzoate" indicates the presence of a benzoate group, which is an ester of benzoic acid.

Description of raw materials used in production

• p-Hydroxybenzoic Acid - An aromatic compound that is the primary precursor of methylparaben.
• Methanol - Used as an alkylating agent to esterify the p-hydroxybenzoic acid.
• Catalyst - For example, sulfuric acid, which accelerates the esterification reaction.

Step-by-step summary of industrial chemical synthesis process.

• Mixing - The p-hydroxybenzoic acid and methanol are mixed together.
• Esterification - The mixture is heated in the presence of a catalyst to form the methyl ester of p-hydroxybenzoic acid.
• Cooling and Separation - The reacted mixture is cooled and the formed product separates.
• Purification - The crude product is purified through techniques such as distillation or crystallization.
• Drying - Moisture is removed from the product.
• Packaging - Methyl p-hydroxybenzoate is packaged in suitable containers for transport and sale.
• Quality Control - The final product undergoes various quality checks to ensure it meets specifications.

Appears in the form of a white powder. Stable. Incompatible with strong bases and strong oxidising agents.

What it is used for and where

Food

Preservative. It is labelled with the number E218 in the list of European food additives as a preservative. Although this allergen is being used less and less, warning should be given because it is labelled under different nomenclature, with different names corresponding to its many synonyms.

Cosmetics

A preservative belonging to the paraben family, a class of chemical compounds to which the scientific literature attributes endocrine disrupting characteristics. Although this allergen is less and less used, warning must be given because it is written on labels under different nomenclature, with different names corresponding to its many synonyms.

Preservative additive used in various industries and serves to fight bacteria, fungi, yeasts and moulds. Like all esters and salts of the Paraben class, it is also often found in cosmetic, pharmaceutical and food formulations.

It is listed with the number E218 in the European food additives list as a preservative.

Methylparaben (MP) is used to extend the shelf life of industrial chemicals (Cashman and Warshaw, 2005). However, when the skin is exposed to MP, this compound permeates the epidermis and dermis and shows in particular greater permeation than other parabens due to the difference in their lipophilicity ( El Hussein et al., 2007 ). It exhibits several adverse dermatological reactions, such as allergic reaction, the cytotoxic synergistic effect of UV radiation and the development of breast cancer ( Nardelli et al., 2009 , Dagher et al., 2012 ). MP concentrations above 4 mg ml -1 in industrial products are known to be harmful ( Darbre and Harvey, 2008; CIR Expert Group, 2008 ). Although MP persists in the dermis ( El Hussein et al., 2007 ), little is known about its side effects or molecular mechanism in the dermis.

Overall, the results show that MP induces cellular senescence in vitro and in vivo, via the GR-c-Jun-ROS pathway, and MP-induced cellular senescence alters ECM components. Although the treatment doses of MP used in this study seem high compared to the limit of industrial use (CIR Expert Group, 2008), the data provide evidence for the hypothesis that MP overdose may induce alterations in ECM components by concentrating senescent fibroblasts in the dermis (1).

Methylparaben is, like all parabens, a debated component about whose safety many doubts have been raised, in particular because of the damage it would cause to the aquatic environment where it is discharged after use (2).

Exposure to methylparaben has been associated with adverse health outcomes and exposure to ultraviolet rays may amplify its toxicity (3).

To reduce the toxicity of parabens in the aquatic environment, a system called the Fenton process is applied (4).

Clinical studies have suggested that Methylparaben increases breast cancer proliferation and may play a direct role in chemoresistance by modulating stem cell activity (5).

Parabens, but in particular Methylparaben, promotes adipogenesis but suppresses the serum marker of bone formation in vivo and indicates possible negative health consequences (6) and may therefore contribute to obesity (7) furthermore, exposure to parabens is associated with DNA damage, male infertility and endocrine disruption in adults (8).

To counteract and mitigate the negative effects of methylparaben on human health, this study suggests that a polyphenolic compound, rosmarinic acid, may protect against unfavourable health outcomes caused by lifelong human exposure to parabens in cosmetic products (9).

The most relevant studies and their abstracts have been selected to explore this in more depth:

     Methylparaben studies

Typical commercial product characteristics Methylparaben 

Appearance	White crystalline powder
Boiling Point	265.5±13.0°C at 760 mmHg
Melting Point	125-128°C
Flash Point	116.4±12.6°C      280°C
Density	1.2±0.1 g/cm3
Vapor Pressure	0.0±0.6 mmHg at 25°C
Refraction Index	1.547
PSA	46.53000
LogP	1.87
Loss on drying	0.5% max
Acidity	0.1mg/g max
Sulphate Ash	0.1% max
Heavy Metal	10ppm max
Chemical Safety

Price

$2.10 - $10.40/ kg

• Molecular Formula    C₈H₈O₃
• Linear Formula    HOC₆H₄CO₂CH₃
• Molecular Weight  152.15
• CAS   99-76-3 
• UNII    A2I8C7HI9T
• EC Number   202-785-7
• DSSTox Substance ID  DTXSID4022529
• IUPAC  methyl 4-hydroxybenzoate
• InChl=1S/C8H8O3/c1-11-8(10)6-2-4-7(9)5-3-6/h2-5,9H,1H3
• InChl Key      LXCFILQKKLGQFO-UHFFFAOYSA-N
• SMILES   COC(=O)C1=CC=C(C=C1)O
• MDL number  MFCD00002352
• PubChem Substance ID    329815219
• ChEBI  31835
• RTECS  DH2450000
• Beilstein    509801
• FEMA    2710
• RXCUI    29903   
• NSC      406127    3827
• NACRES NA.25 

Synonyms :

• E218
• Sodium Methylparaben
• Methylparaben
• Solparol
• Metilparaidrossibenzoato

• Methyl-4-hydroxybenzoate
• p-Hydroxybenzoic acid methyl ester
• methyl para-hydroxybenzoate
• Metagin
• NIPAGIN
• p-Hydroxybenzoic acid, methyl ester
• p-Hydroxybenzoic methyl ester
• Methyl parasept
• Tegosept M
• 4-Hydroxybenzoic acid methylester
• 4-Hydroxybenzoic Acid Methyl Ester
• 4-(Methoxycarbonyl)phenol
• Methyl parahydroxybenzoate

References_________________________________________________________________________

(1)  Cha HJ, Bae S, Kim K, Kwon SB, An IS, Ahn KJ, Ryu J, Kim HS, Ye SK, Kim BH, An S. Overdosage of methylparaben induces cellular senescence in vitro and in vivo. J Invest Dermatol. 2015 Feb;135(2):609-612. doi: 10.1038/jid.2014.405.

(2) Terasaki M, Abe R, Makino M, Tatarazako N. Chronic toxicity of parabens and their chlorinated by-products in Ceriodaphnia dubia. Environ Toxicol. 2015 May-Jun;30(6):664-73. doi: 10.1002/tox.21944. 

Popa DS, Bolfa P, Kiss B, Vlase L, Păltinean R, Pop A, Cătoi C, Crişan G, Loghin F. Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats. Biomed Environ Sci. 2014 Feb;27(2):85-96. doi: 10.3967/bes2014.021. 

(3) Lee J, Park N, Kho Y, Lee K, Ji K. Phototoxicity and chronic toxicity of methyl paraben and 1,2-hexanediol in Daphnia magna. Ecotoxicology. 2017 Jan;26(1):81-89. doi: 10.1007/s10646-016-1743-6. 

(4) Martins RC, Gmurek M, Rossi AF, Corceiro V, Costa R, Quinta-Ferreira ME, Ledakowicz S, Quinta-Ferreira RM. Application of Fenton oxidation to reduce the toxicity of mixed parabens. Water Sci Technol. 2016 Oct;74(8):1867-1875. doi: 10.2166/wst.2016.374.

(5) Lillo MA, Nichols C, Perry C, Runke S, Krutilina R, Seagroves TN, Miranda-Carboni GA, Krum SA. Methylparaben stimulates tumor initiating cells in ER+ breast cancer models. J Appl Toxicol. 2017 Apr;37(4):417-425. doi: 10.1002/jat.3374.

(6) Hu P, Kennedy RC, Chen X, Zhang J, Shen CL, Chen J, Zhao L. Differential effects on adiposity and serum marker of bone formation by post-weaning exposure to methylparaben and butylparaben. Environ Sci Pollut Res Int. 2016 Nov;23(21):21957-21968. doi: 10.1007/s11356-016-7452-0.

(7) Hu P, Chen X, Whitener RJ, Boder ET, Jones JO, Porollo A, Chen J, Zhao L. Effects of parabens on adipocyte differentiation. Toxicol Sci. 2013 Jan;131(1):56-70. doi: 10.1093/toxsci/kfs262.

(8) Baker BH, Wu H, Laue HE, Boivin A, Gillet V, Langlois MF, Bellenger JP, Baccarelli AA, Takser L. Methylparaben in meconium and risk of maternal thyroid dysfunction, adverse birth outcomes, and Attention-Deficit Hyperactivity Disorder (ADHD). Environ Int. 2020 Jun;139:105716. doi: 10.1016/j.envint.2020.105716.

(9) Matwiejczuk N, Galicka A, Zaręba I, Brzóska MM. The Protective Effect of Rosmarinic Acid Against Unfavorable Influence of Methylparaben and Propylparaben on Collagen in Human Skin Fibroblasts. Nutrients. 2020 May 1;12(5):1282. doi: 10.3390/nu12051282.