METHYL p-HYDROXYBENZOATE

Relevant Data

Food Additives Approved in the United States

METHYL P-HYDROXYBENZOATE [show][hide]

Mainterm METHYL P-HYDROXYBENZOATE

Doc Type ASP

CAS number 99-76-3

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Food Additives Approved by European Union:

General Information

Synonyms:	METHYL p-OXYBENZOATE, METHYLPARABEN
Chemical Names:	METHYL p-HYDROXYBENZOATE; METHYL ESTER OF p-HYDROXYBENZOIC ACID
CAS number:	99-76-3
FEMA number:	2710
INS:	218
Functional Class:	Food Additives PRESERVATIVE

From apps.who.int

Evaluations

Evaluation year:	1973
ADI:	0-10 mg/kg bw
Meeting:	17
Specs Code:	R (1995)
Comments:	Group ADI as the sum of the ethyl and methyl esters of p-hydroxybenzoic acid. In view of the adverse effects in male rats, propyl paraben (propyl p-hydroxybenzoate) was excluded from the group ADI for the parabens used in food (TRS 940-JECFA 67/30, 2006)
Report:	NMRS 53/TRS 539-JECFA 17/17
Tox Monograph:	FAS 5/NMRS 53A-JECFA 17/81
Specification:	COMPENDIUM ADDENDUM 6/FNP 52 Add.6/85 (1998). R; FAO JECFA Monographs 1 vol.2/353

From apps.who.int

GSFA Provisions for METHYL p-HYDROXYBENZOATE

Number	Food Category	Max Level	Notes
14.2.7	Aromatized alcoholic beverages (e.g. beer, wine and spirituous cooler-type beverages, low alcoholic refreshers)	1,000 mg/kg	Note 27,Note 224
04.1.2.7	Candied fruit	1,000 mg/kg	Note 27
01.6.5	Cheese analogues	500 mg/kg	Note 27
05.3	Chewing gum	1,500 mg/kg	Note 27
14.2.2	Cider and perry	200 mg/kg	Note 27
05.1.3	Cocoa-based spreads, including fillings	300 mg/kg	Note XS86,Note 27
14.1.5	Coffee, coffee substitutes, tea, herbal infusions, and other hot cereal and grain beverages, excluding cocoa	450 mg/kg	Note 27,Note 160
05.2	Confectionery including hard and soft candy, nougats, etc. other than food categories 05.1, 05.3 and 05.4	1,000 mg/kg	Note 27,Note XS309R
01.7	Dairy-based desserts (e.g. pudding, fruit or flavoured yoghurt)	120 mg/kg	Note 27
05.4	Decorations (e.g. for fine bakery wares), toppings (non-fruit) and sweet sauces	300 mg/kg	Note 27
04.1.2.2	Dried fruit	800 mg/kg	Note 27
08.4	Edible casings (e.g. sausage casings)	36 mg/kg	Note 27
02.3	Fat emulsions mainly of type oil-in-water, including mixed and/or flavoured products based on fat emulsions	300 mg/kg	Note 27
02.2.2	Fat spreads, dairy fat spreads and blended spreads	300 mg/kg	Note 27
04.1.2.10	Fermented fruit products	800 mg/kg	Note 27
04.2.2.7	Fermented vegetable (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera) and seaweed products, excluding fermented soybean products of food categories 06.8.6, 06.8.7, 12.9.1, 12.9.2.1 and 12.9.2.3	300 mg/kg	Note 27
07.2	Fine bakery wares (sweet, salty, savoury) and mixes	300 mg/kg	Note 27
04.1.2.11	Fruit fillings for pastries	800 mg/kg	Note 27
04.1.2.3	Fruit in vinegar, oil, or brine	250 mg/kg	Note 27
04.1.2.8	Fruit preparations, including pulp, purees, fruit toppings and coconut milk	800 mg/kg	Note 27
04.1.2.9	Fruit-based desserts, including fruit-flavoured water-based desserts	800 mg/kg	Note 27
04.1.2.6	Fruit-based spreads (e.g. chutney) excluding products of food category 04.1.2.5	1,000 mg/kg	Note 27
05.1.5	Imitation chocolate, chocolate substitute products	300 mg/kg	Note 27
04.1.2.5	Jams, jellies, marmelades	250 mg/kg	Note 27
14.2.5	Mead	200 mg/kg	Note 27
12.4	Mustards	300 mg/kg	Note 27
11.4	Other sugars and syrups (e.g. xylose, maple syrup, sugar toppings)	100 mg/kg	Note 27
01.6.4	Processed cheese	300 mg/kg	Note 27
15.2	Processed nuts, including coated nuts and nut mixtures (with e.g. dried fruit)	300 mg/kg	Note 27
12.6	Sauces and like products	1,000 mg/kg	Note 27
09.3	Semi-preserved fish and fish products, including mollusks, crustaceans, and echinoderms	1,000 mg/kg	Note 27
15.1	Snacks - potato, cereal, flour or starch based (from roots and tubers, pulses and legumes)	300 mg/kg	Note 27
04.2.2.6	Vegetable (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), seaweed, and nut and seed pulps and preparations (e.g. vegetable desserts and sauces, candied vegetables) other than food category 04.2.2.5	1,000 mg/kg	Note 27
04.2.2.5	Vegetable (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), seaweed, and nut and seed purees and spreads (e.g., peanut butter)	1,000 mg/kg	Note 27
04.2.2.3	Vegetables (including mushrooms and fungi, roots and tubers, pulses and legumes, and aloe vera), and seaweeds in vinegar, oil, brine, or soybean sauce	1,000 mg/kg	Note 27
12.3	Vinegars	100 mg/kg	Note 27
14.1.4	Water-based flavoured drinks, including "sport," "energy," or "electrolyte" drinks and particulated drinks	500 mg/kg	Note 27
14.2.4	Wines (other than grape)	200 mg/kg	Note 27

From www.fao.org

Computed Descriptors

Download SDF

2D Structure
CID	7456
IUPAC Name	methyl 4-hydroxybenzoate
InChI	InChI=1S/C8H8O3/c1-11-8(10)6-2-4-7(9)5-3-6/h2-5,9H,1H3
InChI Key	LXCFILQKKLGQFO-UHFFFAOYSA-N
Canonical SMILES	COC(=O)C1=CC=C(C=C1)O
Molecular Formula	C8H8O3
Wikipedia	methylparaben

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	152.149
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Complexity	136.0
CACTVS Substructure Key Fingerprint	A A A D c c B w M A A A A A A A A A A A A A A A A A A A A A A A A A A w A A A A A A A A A A A B A A A A G g A A C A A A D A S A m A I y D o A A B g C I A i D S C A A C A A A k I A A I i A E G C M g I J j K C N R q A c Q A k w B E I u Y e I 7 C z O I A A A A A A A A A B A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area	46.5
Monoisotopic Mass	152.047
Exact Mass	152.047
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	11
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.7427
Human Intestinal Absorption	HIA+	0.9887
Caco-2 Permeability	Caco2+	0.8682
P-glycoprotein Substrate	Non-substrate	0.7105
P-glycoprotein Inhibitor	Non-inhibitor	0.9617
P-glycoprotein Inhibitor	Non-inhibitor	0.9644
Renal Organic Cation Transporter	Non-inhibitor	0.8791
Distribution
Subcellular localization	Mitochondria	0.9255
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.7458
CYP450 2D6 Substrate	Non-substrate	0.9172
CYP450 3A4 Substrate	Non-substrate	0.6947
CYP450 1A2 Inhibitor	Non-inhibitor	0.6776
CYP450 2C9 Inhibitor	Non-inhibitor	0.9764
CYP450 2D6 Inhibitor	Non-inhibitor	0.9848
CYP450 2C19 Inhibitor	Non-inhibitor	0.9503
CYP450 3A4 Inhibitor	Non-inhibitor	0.9761
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.9640
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9493
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.9791
AMES Toxicity	Non AMES toxic	0.9133
Carcinogens	Non-carcinogens	0.8321
Fish Toxicity	High FHMT	0.7015
Tetrahymena Pyriformis Toxicity	High TPT	0.8900
Honey Bee Toxicity	High HBT	0.8502
Biodegradation	Ready biodegradable	0.8781
Acute Oral Toxicity	III	0.8243
Carcinogenicity (Three-class)	Non-required	0.5851

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-1.8579	LogS
Caco-2 Permeability	1.1158	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	1.8917	LD50, mol/kg
Fish Toxicity	1.9309	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.0748	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	None
Mechanism of Toxicity	None
Metabolism	None
Toxicity Values	None
Lethal Dose	None
Carcinogenicity (IARC Classification)	No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level	None
Health Effects	None
Treatment	None
Reference	Gupta S, Kaisheva E: Development of a multidose formulation for a humanized monoclonal antibody using experimental design techniques. AAPS PharmSci. 2003;5(2):E8.[12866935 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Benzenoids
Class	Benzene and substituted derivatives
Subclass	Benzoic acids and derivatives
Intermediate Tree Nodes	Benzoic acid esters - p-Hydroxybenzoic acid esters
Direct Parent	p-Hydroxybenzoic acid alkyl esters
Alternative Parents	Organic oxides Monocarboxylic acids and derivatives Methyl esters Hydrocarbon derivatives 1-hydroxy-2-unsubstituted benzenoids Organooxygen compounds Benzoyl derivatives
Molecular Framework	Aromatic homomonocyclic compounds
Substituents	P-hydroxybenzoic acid alkyl ester - Benzoyl - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Methyl ester - Carboxylic acid ester - Monocarboxylic acid or derivatives - Carboxylic acid derivative - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Aromatic homomonocyclic compound
Description	This compound belongs to the class of organic compounds known as p-hydroxybenzoic acid alkyl esters. These are aromatic compounds containing a benzoic acid, which is esterified with an alkyl group and para-substituted with a hydroxyl group.

From ClassyFire

Targets

Target Details

Xanthine dehydrogenase/oxidase

General Function:: Xanthine oxidase activity
Specific Function:: Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:: XDH
Uniprot ID:: P47989
Molecular Weight:: 146422.99 Da

References

Cioffi G, D'Auria M, Braca A, Mendez J, Castillo A, Morelli I, De Simone F, De Tommasi N: Antioxidant and free-radical scavenging activity of constituents of the leaves of Tachigalia paniculata. J Nat Prod. 2002 Nov;65(11):1526-9. [12444671 ]

Target Details

Carbonic anhydrase 1

General Function:: Zinc ion binding
Specific Function:: Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:: CA1
Uniprot ID:: P00915
Molecular Weight:: 28870.0 Da

References

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT: Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. Bioorg Med Chem. 2013 Mar 15;21(6):1564-9. doi: 10.1016/j.bmc.2012.05.019. Epub 2012 May 17. [22668600 ]

Target Details

Carbonic anhydrase 12

General Function:: Zinc ion binding
Specific Function:: Reversible hydration of carbon dioxide.
Gene Name:: CA12
Uniprot ID:: O43570
Molecular Weight:: 39450.615 Da

References

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT: Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. Bioorg Med Chem. 2013 Mar 15;21(6):1564-9. doi: 10.1016/j.bmc.2012.05.019. Epub 2012 May 17. [22668600 ]

Target Details

Carbonic anhydrase 14

General Function:: Metal ion binding
Specific Function:: Reversible hydration of carbon dioxide.
Gene Name:: CA14
Uniprot ID:: Q9ULX7
Molecular Weight:: 37667.37 Da

References

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT: Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. Bioorg Med Chem. 2013 Mar 15;21(6):1564-9. doi: 10.1016/j.bmc.2012.05.019. Epub 2012 May 17. [22668600 ]

Target Details

Carbonic anhydrase 2

General Function:: Zinc ion binding
Specific Function:: Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:: CA2
Uniprot ID:: P00918
Molecular Weight:: 29245.895 Da

References

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT: Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. Bioorg Med Chem. 2013 Mar 15;21(6):1564-9. doi: 10.1016/j.bmc.2012.05.019. Epub 2012 May 17. [22668600 ]

Target Details

Carbonic anhydrase 7

General Function:: Zinc ion binding
Specific Function:: Reversible hydration of carbon dioxide.
Gene Name:: CA7
Uniprot ID:: P43166
Molecular Weight:: 29658.235 Da

References

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT: Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. Bioorg Med Chem. 2013 Mar 15;21(6):1564-9. doi: 10.1016/j.bmc.2012.05.019. Epub 2012 May 17. [22668600 ]

Target Details

Carbonic anhydrase 9

General Function:: Zinc ion binding
Specific Function:: Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
Gene Name:: CA9
Uniprot ID:: Q16790
Molecular Weight:: 49697.36 Da

References

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT: Mono-/dihydroxybenzoic acid esters and phenol pyridinium derivatives as inhibitors of the mammalian carbonic anhydrase isoforms I, II, VII, IX, XII and XIV. Bioorg Med Chem. 2013 Mar 15;21(6):1564-9. doi: 10.1016/j.bmc.2012.05.019. Epub 2012 May 17. [22668600 ]

Target Details

Peroxisome proliferator-activated receptor gamma

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:: PPARG
Uniprot ID:: P37231
Molecular Weight:: 57619.58 Da

References

Pereira-Fernandes A, Demaegdt H, Vandermeiren K, Hectors TL, Jorens PG, Blust R, Vanparys C: Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect. PLoS One. 2013 Oct 14;8(10):e77481. doi: 10.1371/journal.pone.0077481. eCollection 2013. [24155963 ]

From T3DB

Mainterm	METHYL P-HYDROXYBENZOATE
Doc Type	ASP
CAS number	99-76-3

Chemical name	Methyl p-hydroxybenzoate
CAS number	99-76-3
E No.	E 218
INS	218
Group	No
Component of the group	Sorbic acid - sorbates; p-hydroxybenzoates (E 200 - 203; 214 - 219) Sorbic acid - sorbates; Benzoic acid - benzoates; p-hydroxybenzoates (E 200 - 219) p-hydroxybenzoates (PHB) (E 214 - 219)