Relevant Data

Food Additives Approved in the United States

Flavouring Substances Approved by European Union:

  • Ethyl 4-hydroxybenzoate [show]

Food Additives Approved by European Union:

  • Ethyl-p-hydroxybenzoate [show]

General Information

Synonyms: ETHYL p-OXYBENZOATE, ETHYLPARABEN
Chemical Names: ETHYL ESTER OF p-HYDROXYBENZOIC ACID; ETHYL p-HYDROXYBENZOATE
CAS number: 120-47-8
INS:

214

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.6/57 (1998). R; FAO JECFA Monographs 1 vol.2/23

From apps.who.int



GSFA Provisions for ETHYL 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 224,Note 27
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 160,Note 27
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 XS309R,Note 27
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


Toxicity Profile

Route of ExposureNone
Mechanism of ToxicityNone
MetabolismNone
Toxicity ValuesNone
Lethal DoseNone
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelNone
Health EffectsNone
TreatmentNone
Reference

From T3DB


Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
  1. 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 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA12
Uniprot ID:
O43570
Molecular Weight:
39450.615 Da
References
  1. 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 ]
General Function:
Metal ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA14
Uniprot ID:
Q9ULX7
Molecular Weight:
37667.37 Da
References
  1. 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 ]
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
  1. 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 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA7
Uniprot ID:
P43166
Molecular Weight:
29658.235 Da
References
  1. 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 ]
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
  1. 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 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
References
  1. Watanabe Y, Kojima H, Takeuchi S, Uramaru N, Ohta S, Kitamura S: Comparative study on transcriptional activity of 17 parabens mediated by estrogen receptor alpha and beta and androgen receptor. Food Chem Toxicol. 2013 Jul;57:227-34. doi: 10.1016/j.fct.2013.03.036. Epub 2013 Apr 6. [23567241 ]

From T3DB