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ETHYLPARABEN

Hazardous Substances DataBank Number
938
Related PubChem Records
Related CIDs

1 Human Health Effects

1.1 Toxicity Summary

IDENTIFICATION AND USE: Ethylparaben forms small colorless crystals, or white powder. Ethylparaben inhibits the growth of fungi and bacteria and is used as a preservative for pharmaceuticals, adhesives, and various cosmetic preparations. HUMAN EXPOSURE AND TOXICITY: Ethylparaben was a skin irritant in man. It gave no evidence of sensitizing potential in a human study. The paraben esters as a generic class are rare sensitizers when applied to the intact skin of man. Application to the damaged skin is a more common cause of sensitization. A methyl:ethyl:propylparaben mixture has been shown on oral administration to exacerbate pre-existing skin complaints. ANIMAL STUDIES: Ethylparaben was an eye irritant in rabbits. A low acute oral toxicity has been demonstrated for ethylparaben in laboratory animals. Limited long-term studies in rats have also indicated a low toxicity and have generated no evidence of carcinogenic activity. Ethylparaben in the diet produced cell proliferation in the forestomach of rats. No evidence of mutagenicity was reported in limited Ames Bacterial tests. Ethylparaben did increase chromosomal aberrations in a Chinese Hamster ovary cell assay, but similar effects were not seen in rats treated with ethylparaben. Fetal toxicity at maternally toxic dose levels occurred in female rats treated orally during pregnancy. Ethylparaben was nonteratogenic in rats. In one in vitro study, sperm were not viabile at concentrations as low as 8 mg/mL for Ethylparaben, but an in vivo study of 0.1% or 1.0% for Ethylparaben in the diet of mice reported no spermatotoxic effects.

1.2 Human Toxicity Excerpts (Complete)

/HUMAN EXPOSURE STUDIES/ Methylparaben, Ethylparaben, Propylparaben, and Butylparaben were each applied to the backs of 50 humans at concentrations of 5, 7, 10, 12, and 15 % in propylene glycol. Test compounds were applied daily for 5 days, and patches were then removed and the sites scored. The concentrations of individual Parabens that produced no irritation were Methylparaben, 5%; Ethylparaben, 7%; Propylparaben, 12%; and Butylparaben, 5%. Higher concentrations produced some evidence of irritation. In a repeated insult patch test (RIPT), each Paraben at the "no effect" concentration above was applied to the skin of 50 subjects (25M/25F) for 4 to 8 hrs every other day for 3 weeks (10 applications). Following a 3-week rest, the materials were reapplied at induction concentrations for 24 to 48 hrs. No sensitization was reported.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 56. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/HUMAN EXPOSURE STUDIES/ Methylparaben and Ethylparaben, in increasing concentrations, were studied for their effect on the oral mucous membrane of 39 subjects. They described toxic limit concentrations for Methylparaben and Ethylparaben of 5 and 10 %, respectively. One subject had a reaction of the oral mucous membrane to Methylparaben.
Cosmetic Ingredient Review; Final Report of the Cosmetic Ingredient Review Expert Panel; Amended Safety Assesment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben; p. 57, June 2006.
/SIGNS AND SYMPTOMS/ ... Ethyl paraben may cause occasional hypersensitivity, usually manifested as dermatitis.
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1090
/SIGNS AND SYMPTOMS/ Ointments containing ethyl paraben can cause redness and swelling of eyelids from allergic contact dermatitis. Ingestion of a 0.03% aqueous ethyl paraben solution has caused irritation to the intestinal mucosa and a "feltlike" sensation in the mouth.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:668
/SIGNS AND SYMPTOMS/ ... As constituents of antibacterial ointments, dermatological preparations, and proprietary lotions and skin creams ... /parabens/ are recognized causes of severe and intractable contact dermatitis ... Patients sensitive to one paraben show cross-sensitivity to the others. /Parabens/
Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 969
/SIGNS AND SYMPTOMS/ All ... parabens are capable of sensitizing skin and inducing cutaneous allergic responses, although incidence of such reactions is low. ... /Methylparaben/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1096
/SIGNS AND SYMPTOMS/ /Parabens/ ... are often incorporated in ... creams, lotions, and ointments that may be used in region of eyes, and occasionally cause redness and swelling of eyelids from allergic contact dermatitis. /Parabens/
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 695
/ALTERNATIVE and IN VITRO TESTS/ Potent in vitro spermicidal activity of parabens against human spermatozoa was demonstrated in this study. The "pass" point concentration of the four parabens--methylparaben, ethylparaben, propylparaben, and butylparaben, at which all spermatozoa were immobilized and no immobilized spermatozoon revived after 30 min incubation in phosphate buffered glucose solution, was 6, 8, 3, and 1 mg/mL, respectively, as tested by Harris' method. These parabens are used as food and pharmaceutic preservatives; less toxicity and side effects were expected for the development of parabens as vaginal contraceptive agents.
Song BL et al; Contraception 39 (3): 331-5 (1989)
/ALTERNATIVE and IN VITRO TESTS/ ... The estrogenic effects of four parabens (methylparaben, ethylparaben, n-propylparaben, n-butylparaben) in estrogen-dependent MCF7 human breast cancer cells /are reported/. Competitive inhibition of 3-H-estradiol binding to MCF7 cell estrogen receptors could be detected at 1,000,000-fold molar excess of n-butylparaben (86%), n-propylparaben (77%), ethyl-paraben (54%) and methylparaben (21%). At concentrations of 10-6 M and above, parabens were able to increase expression of both transfected (ERE-CAT reporter gene) and endogenous (pS2) estrogen-regulated genes in these cells. They could also increase proliferation of the cells in monolayer culture, which could be inhibited by the antiestrogen ICI 182,780, indicating that the effects were mediated through the estrogen receptor. However, no antagonist activity of parabens could be detected on regulation of cell proliferation by 17beta-estradiol at 10-10 M. Molecular modeling has indicated the mode by which paraben molecules can bind into the ligand binding pocket of the crystal structure of the ligand binding domain (LBD) of the estrogen receptor alpha (ERalpha) in place of 17beta-estradiol; it has furthermore shown that two paraben molecules can bind simultaneously in a mode in which their phenolic hydroxyl groups bind similarly to those of the meso-hexoestrol molecule ...
Byford JR et al; J Steroid Biochem Mol Biol 80 (1): 49-60 (2002)
/ALTERNATIVE and IN VITRO TESTS/ Estrogenic activities of the phenolic preservatives methylparaben, ethylparaben, propylparaben, butylparaben, isopropylparaben and isobutylparaben were examined by assaying estrogen-receptor (ER)-dependent proliferation of MCF-7 cells. All the compounds stimulated the proliferation to about the same level as the maximal cell yield attained with 3x10-11 M 17beta-estradiol, but at a concentration in the order of 10+5 to 10+7 higher than 17beta-estradiol. The cell-proliferative effects of parabens were completely suppressed by anti-estrogen ICI 182,780. MCF-7 cells treated with butylparaben and isobutylparaben exhibited a decrease in gene expression of ERalpha and an increase in that of progesterone-receptor (PR), but the effects of these parabens were not as prominent as those of 17beta-estradiol. Western blot analysis indicated that these parabens caused a slight decrease in expression of ERalpha protein. Competitive binding to human ERalpha and ERbeta in vitro revealed that the parabens with longer side-chains showed greater affinity for estrogen receptors, and that they had similar relative binding affinity (RBA) values to both ERalpha and ERbeta. RBA values were much smaller than that of diethylstilbestrol. In conclusion, parabens have ER-dependent estrogenic activities, and their effects on the intracellular signaling pathway might be different from that of 17beta-estradiol.
Okubo T et al; Food Chem Toxicol 39 (12): 1225-1232 (2001)
/ALTERNATIVE and IN VITRO TESTS/ In this work, the estrogenic effects of three classes of substances included in cosmetic formulations-parabens, ultraviolet (UV) screens, and musk fragrances-were studied. Their estrogenic activity was measured with the use of three reporter cell lines: HELN, HELN ERalpha, and HELN ERbeta. These three cell lines allowed for the measurement of estrogenic activity toward estrogen receptors alpha and beta (ERalpha and ERbeta, while taking nonspecific interactions into account. Eight of the 15 substances tested showed specific estrogenic activity with the following degree of potency on ERalpha butylparaben > propylparaben > homosalate = octyl-dimethyl-PABA = 4-methyl-benzylidenecamphor = octyl-methoxycinnamate > ethylparaben = galaxolide. Among these active substances, parabens activated ERalpha and ERbeta similarly ... Methylparaben, ethylparaben, musk moskene, celestolide, and cashmeran did not activate estrogenic responses up to 10(-5) M.
Gomez E et al; J Toxicol Environ Health A 68 (4): 239-51 (2005)
/ALTERNATIVE and IN VITRO TESTS/ ... The doses of methylparaben, ethylparaben, and propylparaben that produced 50% cell inhibition (IC50) in HeLa cells were 1.3, 0.6, and 0.22 mM, respectively. ... In HeLa cells, parabens induced jagged cell shapes; cell processes were shortened, branched, rough-edged, and curved. Many perinuclear and cytoplasmic granules were also observed. The authors stated that growth inhibition of bacteria by parabens was due to inhibition of cellular uptake of amino acids and other compounds needed for substrate and energy supply.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 30. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/ALTERNATIVE and IN VITRO TESTS/ An in vitro test was set up to assess the release of lysosomal enzymes from cells and the effect on this process of the commonly used preservatives, parabens. Human peripheral lymphocytes, cultivated in vitro for 24 hr in the presence or absence of phytohemagglutinin (PHA; 5 mg/L), were used. After 1 day of incubation, PHA treatment caused an increased release (from 220 to 500%) of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-L-fucosidase and alpha-D-galactosidase. This enhancement was analytically reliable, and detectable with 1-5 ug of cell protein. Leakage of lactate dehydrogenase (LDH) underwent only a 20% increase on PHA treatment, indicating that the increased release of lysosomal enzymes was presumably due to secretion, not to cell damage. In PHA-stimulated lymphocytes, methyl-, ethyl-, propyl- and butyl-parabens caused a concentration-dependent diminution of the secretion of lysosomal enzymes. Butyl-paraben appeared to be the most potent inhibitor, causing a 45-50% inhibition at 0.06 mmol/L. ... Parabens did not influence the release of LDH, suggesting that they affected particularly the secretion of lysosomal enzymes. ...
Bairati C et al; Clin Chim Acta 224 (2): 147-57 (1994)
/ALTERNATIVE and IN VITRO TESTS/ A body of epidemiological evidence implicates exposure to endocrine disrupting chemicals (EDCs) with increased susceptibility to breast cancer. To evaluate the physiological effects of a suspected EDC in vivo, we exposed MCF-7 breast cancer cells and a patient-derived xenograft (PDX, estrogen receptor positive) to physiological levels of methylparaben (mePB), which is commonly used in personal care products as a preservative. mePB pellets (4.4 ug per day) led to increased tumor size of MCF-7 xenografts and ER+ PDX tumors. mePB has been thought to be a xenoestrogen; however, in vitro exposure of 10 nM mePB failed to increase MCF-7 cell proliferation or induction of canonical estrogen-responsive genes (pS2 and progesterone receptor), in contrast to 17beta-estradiol (E2) treatment. MCF-7 and PDX-derived mammospheres exhibited increased size and up-regulation of canonical stem cell markers ALDH1, NANOG, OCT4 and SOX2 when exposed to mePB; these effects were not observed for MDA-MB-231 (ER- ) mammospheres. As tumor-initiating cells (TICs) are also believed to be responsible for chemoresistance, mammospheres were treated with either tamoxifen or the pure anti-estrogen fulvestrant in the presence of mePB. Blocking the estrogenic response was not sufficient to block NANOG expression in mammospheres, pointing to a non-classic estrogen response or an ER-independent mechanism of mePB promotion of mammosphere activity. Overall, these results suggest that mePB increases breast cancer tumor proliferation through enhanced TIC activity, in part via regulation of NANOG, and that mePB may play a direct role in chemoresistance by modulating stem cell activity.
Lillo MA et al; J Appl Toxicol doi: 10.1002/jat.3374 (2016) (Epub ahead of print)
/ALTERNATIVE and IN VITRO TESTS/ In vitro, ethyl paraben is a potent spermicidal agent against human spermatozoa. After treatment with 8 mg/mL ethyl paraben, all spermatozoa were immobilized for 30 min.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:668
/OTHER TOXICITY INFORMATION/ Ethylparaben was a skin irritant in man and an eye irritant in rabbits. It gave no evidence of sensitizing potential in a human study. The paraben esters as a generic class are rare sensitizers when applied to the intact skin of man. Application to the damaged skin is a more common cause of sensitization. A methyl:ethyl:propylparaben mixture has been shown on oral administration to exacerbate pre-existing skin complaints. A low acute oral toxicity has been demonstrated for ethylparaben in laboratory animals. Limited long-term studies in rats have also indicated a low toxicity and have generated no evidence of carcinogenic activity. No evidence of mutagenicity was reported in limited Ames Bacterial tests. Chromosomal damage was induced in mammalian cells in culture, but similar effects were evidently not seen in rats treated with ethylparaben. Fetal toxicity at maternally toxic dose levels occurred in female rats treated orally during pregnancy.
BIBRA working group; Toxicity profile. The British Industrial Biological Research Association p.7 (1989)

1.3 Skin, Eye, and Respiratory Irritations

... when tested using Human Patch tests (undiluted material) only a limited number of people developed mild skin irritation.
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2928

1.4 Body Burden (Complete)

Ethylparaben concentrations below the quantitation limit (0.02 ng/mL) to 2.69 ng/mL and 0.11-31.7 ng/mL in urine samples from children from the United States and China, respectively. Levels in adults were below the quantitation limit to 47.5 ng/mL and below the quantitation limit to 119 ng/mL, respectively(1). Ethylparaben had a frequency of detection of 58% in urine samples from a group of US male and female adults sampled from 2003 to 2005(2).
(1) Wang L et al; Environ Sci Technol 47: 2069-76 (2013)
(2) Ye X et al; Environ Health Perspect 114(12): 1843-46 (2006)

1.5 Average Daily Intake (Complete)

Estimated daily intakes of ethylparaben from indoor dust (13 cities, 4 countries) from the United States, China, Korea and Japan (all ng/kg bw/day)(1).
Population
Infants
USA
0.09
China
Not reported
Korea
Not reported
Japan
Not reported
Population
Toddlers
USA
0.10
China
Not reported
Korea
Not reported
Japan
Not reported
Population
Children
USA
0.05
China
0.02
Korea
0.12
Japan
0.21
Population
Teenagers
USA
0.02
China
Not reported
Korea
Not reported
Japan
Not reported
Population
Adults
USA
0.008
China
0.004
Korea
0.02
Japan
0.047
(1) Wang L et al; Environ Sci Technol 46: 11584-93 (2012)

2 Emergency Medical Treatment

2.1 Antidote and Emergency Treatment (Complete)

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160-1

3 Animal Toxicity Studies

3.1 Non-Human Toxicity Excerpts (Complete)

/LABORATORY ANIMALS: Acute Exposure/ All parabens produced same toxicity symptoms in mice--rapid onset of ataxia, paralysis and deep depression resembling anesthesia. Only rarely was there evidence of increased motor activity. ...Where death occurred, it was usually within 1 hr. /Parabens/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 126
/LABORATORY ANIMALS: Acute Exposure/ ... Slight irritation to the rabbit eye.
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2928
/LABORATORY ANIMALS: Acute Exposure/ Products containing 0.2% Ethylparaben produced no deaths when administered to groups of five rats at a dose of 15 g/kg.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 34. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Acute Exposure/ Occular irritation: Ethylparaben at 100% instilled into the eyes of two groups of six albino rabbits was slightly irritating, with a maximum eye irritation score of 2/110 on Day 1. Ethylparaben at 10% in water produced no signs of irritation.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 40. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Acute Exposure/ Ethylparaben was tested for acute oral toxicity as a 20% dilution in propylene glycol. Doses of 4.64 g/kg or 2.15 g/kg were administered by gastric intubation to groups of five female rats. Three deaths resulted from administration of the higher dose and none from the lower dose. There were no gross lesions at necropsy on the seventh day. The acute oral LD was 4.30 g/kg.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 34. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Acute Exposure/ The Draize skin irritation technique was used to test Ethylparaben at 100% and at 10% in water on groups of nine rabbits. The undiluted and diluted ingredient produced no signs of irritation. ... Products containing 0.2% Ethylparaben produced minimal to mild irritation with primary (skin\eye) irritation scores (PII) of 0.17 to 0.56.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 39. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Ethylparaben or butylparaben were fed to /24/ rats at concentrations of 2 or 8% in the diet for 12 weeks. Negative controls were included in the study. ...At 8% dietary concentration, ethylparaben reduced growth rate, decreased motor activity, and, in some cases, caused death within the first week. All males fed 8% butylparaben died before the twelfth week. Females fed this diet exhibited signs of toxicity.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 38. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Methylparaben, ethylparaben, propylparaben, and butylparaben (at 0.1%) were each injected intracutaneously into the shaved dorsal skin of 10 guinea pigs per ingredient according to the Draize method. Injections were made three times weekly for 3 weeks (10 injections). Two weeks after the final induction injection, a challenge injection was administered into an adjacent site and observed 24 hours later. There were no reactions in the animals to any of the parabens. It was observed that these ingredients are nonsensitizing.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 40. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ A Magnusson-Kligman guinea pig maximization test was used to determine the sensitization potentials of methylparaben and ethylparaben. The procedure calls for a protocol of induction with methylparaben or ethylparaben at 1% and 5% in 50% Freund's complete adjuvant, booster of 10% sodium lauryl sulfate followed by 50% of the relevant paraben in petrolatum 24 h later, and challenge with methylparaben at 5% and 10% and ethylparaben at 1% and 2% in petrolatum. A total of 80 female guinea pigs were used. Phenylacetaldehyde served as a positive control, with 7/8 and 8/8 animals in two groups having a reaction. No animals in any of the methylparaben or ethylparaben groups showed a reaction.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 40. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ After 18 mo of being fed 140 mg/kg of ethyl paraben daily, growth stimulation was noted in rats. Growth retardation occurred in rats fed 1600 mg/kg daily.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:667
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The biological effects of ethyl-p-hydroxybenzoate (EB) were studied using pregnant and non-pregnant Wistar rats. Tests for acute toxicity were performed in 3 groups with EB orally administered at 10%, 1% and 0.1%. Tests for teratogenicity were made in fetuses from 3 groups of pregnant rats with EB given orally in the critical period at these concentrations. Fetal external features were observed, and visceral and osseous conditions were examined. Neonatal growth was observed for 1 mo. after birth in rat pups nursed by mother rats. No noticeable acute toxicity could be identified (200 mg/kg) and there was no sign of teratogenicity identifiable in fetuses at different EB concentrations. From the 10% EB group, some fetuses appeared with low body weight; there were some instances of malformations of bones and viscera attributed to maternal malnutrition. Neonatal growth curves showed no abnormal trends. The administration dose of 0.1% EB (3.9 g/kg) in rats is comparable to 240 g/60 kg body weight for a human adult. EB at these levels caused no significant ill effects in rats.
Moriyama et al; Acta Obstet Gynaecol Jpn 22 (2): 94-106 (1975)
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No teratogenic effects were observed in fetuses of Wistar rats which had received ethyl paraben orally (10%, 1%, or 0.01%). However, body weights were lower in some fetuses of rats which had received 10% ethyl paraben (45,600 mg/kg).
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 668
/ENDOCRINE MODULATION/ ... Evidence of the estrogenicity /of parabens (Pbens)/ using a morphometric analysis of uteri from mice treated with the preservatives methylparaben (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben (BuPben) compared with estradiol (E2) /is presented/. Different groups of adult ovariectomized (Ovx) CD1 mice were subcutaneously (sc) treated daily for three days with two different equimolar doses (362 and 1086 uL/kg) of the Pbens: MePben (55 and 165 mg/kg), EtPben (60 and 180 mg/kg), PrPben (65 and 195 mg/kg), BuPben (70 and 210 mg/kg), E2 (10 ug/kg; 0.036 uL/kg), and vehicle (propyleneglycol; V, 10 mL/kg). On the fourth day, uteri were dissected, blotted, weighed, and placed in a fixative solution for 24 hr. The paraffin embeded uteri were cut to obtain 7 microm thick transversal sections. Luminal epithelium heights (LEH), glandular epithelium heights (GEH), and myometrium widths (MW) were measured. The highest Pbens dose was able to produce uterotrophic effects (38 to 76%) compared to E2 effects (100%). The relative uterotrophic potency to E2 (100) was from 0.02 to 0.009. Significant increases (P<0.05) in LEH, GEH, and MW as compared with V were obtained: LEH from 87 to 113% (E2 153%), GEH from 10 to 40% (E2 60%), and MW from 35 to 43% (E2 88%). These results confirm that Pbens at the doses assayed here induce estrogenic histological changes in the uteri of Ovx mice.
Lemini C et al; Toxicol Ind Health 20 (6-10): 123-32 (2004)
/GENOTOXICITY/ At a concentration of 10 mmol/L, ethyl paraben is mutagenic in Escherichia coli.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 667
/GENOTOXICITY/ ... The results of mutagenicity screening of food additives, including ethylparaben, isopropylparaben and isobutylparaben /are described/. Results of reverse mutation assays using S. typhimurium strains TA 92, TA 1535, TA 100, TA 1537, TA 94, and TA 98 (Ames test) were considered negative (<4.9% mutation frequency) for all three parabens. In chromosomal aberration assays using a Chinese hamster fibroblast cell line, after 48 hr, cells treated with 0.25 mg/mL ethylparaben, 0.125 mg/mL isopropylparaben or 0.6 mg/mL isobutylparaben in ethanol had 1%, 2.0% and 3.0% polyploid cells and a 11%, 1%, and 1% incidence of structural chromosomal aberrations, respectively. The authors stated that the control incidence of aberrations was usually less than 3% and that any result less than 4% was considered negative. A result more than 10% was positive.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 42. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
/ALTERNATIVE and IN VITRO TESTS/ The widely used phenolic preservatives ethylparaben, propylparaben, butylparaben and their common metabolite p-hydroxybenzoic acid were tested for their ability to evoke an estrogenic response in vivo. Yolk protein induction in sexually immature rainbow trout was used as an estrogen-specific endpoint after repeated injections of the compounds. All tested parabens were estrogenic in doses between 100 and 300 mg/kg, while the metabolite showed no activity. Ethylparaben was found to be approximately sixty times weaker than propyl- and butylparaben which had estrogenic potencies comparable to those previously found for bisphenol A.
Pedersen KL et al; Pharmacol Toxicol 86 (3): 110-3 (2000)
/ALTERNATIVE and IN VITRO TESTS/ Evidence /is presented/ for the in vivo and in vitro bioactivities and receptor binding affinities of methylparaben (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben (BuPben) compared with those of estradiol (E2). Estrogenicity was studied using the uterotrophic assay in immature (Im) and adult ovariectomized (Ovx) CD1 mice, and in immature female Wistar rats (IW). Animals were subcutaneously (sc) treated for three consecutive days with different molar equivalent doses ranging from 3.62 to 1086 uL/kg body weight of parabens (Pbens), E2 (0.036 uL/kg), or vehicle. Pbens increased uterine weight in Im and Ovx animals and their relative uterotrophic effect to E2 (100) (RUEE2) were from 34 to 91. The relative uterotrophic potencies related to E2 (100) (RUPE2) of these compounds were from 0.003 to 0.007. The E2 ED50 for CD1 animals able to increase the uterine weight was 7 ug/kg (0.9-55 confidence limits); and that of Pbens ranged from 18 to 74 mg/kg. In IW rats, the ED50 were from 33 to 338 mg/kg. All Pbens, except MePb, competed with [3H]E2 for the estrogen receptor binding sites. The uterotrophic effects of Pbens in Im mice have a positive correlation with the side-chain length of the ester group of these compounds. ... The NOELs values for Pbens uterotrophic activity in Im were from 0.6 to 6.5 mg/kg/day; and Ovx from 6 to 55 mg/kg. The NOELs IW ranged from 16.5 to 70 mg/kg indicating that Im were more susceptible than Ovx and IW to these effects. The data shown here confirm the estrogenicity of Pbens.
Lemini C et al; Toxicol Ind Health 19 (2-6): 69-79 (2003)
/OTHER TOXICITY INFORMATION/ Ethylparaben was a skin irritant in man and an eye irritant in rabbits. It gave no evidence of sensitizing potential in a human study. The paraben esters as a generic class are rare sensitizers when applied to the intact skin of man. Application to the damaged skin is a more common cause of sensitization. A methyl:ethyl:propylparaben mixture has been shown on oral administration to exacerbate pre-existing skin complaints. A low acute oral toxicity has been demonstrated for ethylparaben in laboratory animals. Limited long-term studies in rats have also indicated a low toxicity and have generated no evidence of carcinogenic activity. No evidence of mutagenicity was reported in limited Ames Bacterial tests. Chromosomal damage was induced in mammalian cells in culture, but similar effects were evidently not seen in rats treated with ethylparaben. Fetal toxicity at maternally toxic dose levels occurred in female rats treated orally during pregnancy.
BIBRA working group; Toxicity profile. The British Industrial Biological Research Association p.7 (1989)
/OTHER TOXICITY INFORMATION/ Ethyl gallate, ethylparaben (ethyl 4-hydroxybenzoate), and ethyl protocatechuate (ethyl 3,4-dihydroxybenzoate) were evaluated as hydroxyl radical scavengers in a model system irradiated with simulated sunlight to generate the radicals. All of the compounds showed some hydroxyl radical scavenging properties, with ethyl protocatechuate being the most active under the test conditions. ...
Hall G et al; Pharm Acta Helv 71 (3): 221-4 (1996)

3.2 Ecotoxicity Excerpts (Complete)

/AQUATIC SPECIES/ The acute toxicity of 21 parabens and their chlorinated derivatives was investigated by means of two toxicity bioassays: Daphnia magna immobilization test and the inhibition of bioluminescence of Vibrio fischeri. The median effective concentration (EC(50)) values of the tested parabens ranged from 2.2 to 62 mg/L in the D. magna test and from 0.0038 to 5.9 mg/L in the V. fischeri test at 15 min after exposure. The toxicity of dichlorinated methyl- and n-propylparaben, the most commonly used preservatives in cosmetics, toward D. magna was 3.9- and 2.8-fold that of their corresponding parent compounds. Toxicity toward D. magna showed a linear relationship with log P, indicating that toxicity increases with increasing hydrophobicity. On the other hand, the correlations of toxicity toward V. fischeri with hydrophobicity and with the degree of chlorination were poor. In addition, the results of the present study indicated that the V. fischeri test was more sensitive than the D. magna test for the determination of the acute toxicity of parabens. A complete assessment of the ecological and toxicological risks of parabens may require the examination of chlorinated parabens as well as the parent pollutants, as described in the present study.
Terasaki M et al; J Appl Toxicol 29 (3): 242-7 (2009)
/AQUATIC SPECIES/ The chronic toxicity of 12 compounds of parabens and their chlorinated by-products was investigated using 7-day Ceriodaphnia dubia test under static renewal condition in order to generate information on how to disinfect by-products of preservatives that are discharged in aquatic systems. The mortality and inhibition of reproduction tended to increase with increasing hydrophobicity and decreased with the degree of chlorination of parabens. The EC50 values for mortality, offspring number, and first brood production ranged between 0.30-3.1, 0.047-12, and 1.3-6.3 mg/L, respectively. For the number of neonates, the most sensitive endpoint, the no-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) values ranged from 0.63 to 10 mg/L and from 1.2 to 19 mg/L, respectively. Methylparaben (MP), benzylparaben (BnP), and dichlorinated BnP (Cl2BnP) elicited a significant decrease in offspring numbers even at their lowest concentration tested; the NOEC for these compounds was determined to be less than the lowest test concentration (1.3, 0.04, and 0.63 mg/L for MP, BnP, and Cl2BnP, respectively). Propylparaben (PP), chlorinated PP, isopropylparaben (iPP), and chlorinated iPP exhibited nonmonotonic concentration-dependent response; their NOEC and LOEC values could not be determined. The multivariate approach involving principal component analysis and hierarchical cluster analysis revealed four groups that corresponded to the toxicological profiles of parabens. Our results suggested that disinfection of parabens by chlorination could reduce aquatic toxicity of original compounds. The findings obtained in our study together with the data available on paraben concentrations in aquatic systems can be used to perform preliminary risk assessment by comparing the predicted environmental concentration (PEC) with the predicted no-effect concentration (PNEC) for the marine aquatic environment. The calculated PEC/PNEC ratios ranged from 0.0012 to 0.2, with the highest value observed in MP. This suggested that there are negligible environmental risks for aquatic organisms at current use levels.
Terasaki M et al; Environ Toxicol 30 (6): 664-73 (2015)

3.3 Non-Human Toxicity Values (Complete)

LD50 Rat (female) oral 4.30 g/kg
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 34. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
LD50 Rat oral 11.0 g/kg
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2928
LD50 Guinea pig oral 2.0 g/kg /From table/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 665
LD50 Rabbit oral 5.0 g/kg /From table/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 665
LD50 Rabbit dermal 15.0 g/kg
Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 2928
LD50 Mouse (dd-strain) oral 6008 mg/kg
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 35. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
LD50 Mouse oral 3 g/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2004
LD50 Mouse ip 520 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2004
LD50 Dog oral 5.0 g/kg /From table/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 667

3.4 Ecotoxicity Values (Complete)

EC50; Species: Pseudokirchneriella subcapitata (Green Algae) exponential growth phase; Conditions: freshwater, static; Concentration: 18000 ug/L for 72 hr (95% confidence interval: 17000-19000 ug/L); Effect: population, decreased population growth rate /formulation/
Madsen T et al; Ministry of the Environment and Energy, Danish EPA, Environmental Project No.615: 235 (2001) as cited in the ECOTOX database. Available from, as of October 6, 2016
LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 39000 ug/L for 24 hr (95% confidence interval: 36900-40600 ug/L) />99% purity/
Li MH; Toxicol Environ Chem 94 (3): 566-573 (2012) as cited in the ECOTOX database. Available from, as of October 6, 2016
LC50; Species: Dugesia japonica (Flatworm) body length 0.7 cm; Conditions: freshwater, static, 25 °C; Concentration: 31000 ug/L for 96 hr (95% confidence interval: 30000-31900 ug/L) />99% purity/
Li MH; Toxicol Environ Chem 94 (3): 566-573 (2012) as cited in the ECOTOX database. Available from, as of October 6, 2016

3.5 Ongoing Test Status

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of September 8, 2016: http://actor.epa.gov/dashboard/]

4 Metabolism / Pharmacokinetics

4.1 Metabolism / Metabolites (Complete)

Yields p-hydroxybenzoic acid in pig and in Aspergillus. /from table/
Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976., p. E-11
/Paraben/ ... esters are well absorbed and hydrolysis of ester linkage and metabolic conjugation constitute chief route of elimination /in dogs/. Similar metabolic scheme was observed in man. /Paraben esters/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 126
Urine from cats who had received (14)C-labeled ethyl-p-hydroxybenzoate, orally contained 2 major metabolites, p-hydroxyhippuric acid and free p-hydroxybenzoic acid.
Phillips S et al; Toxicol Lett 2 (4): 237-242 (1978)
In mice, rats, rabbits, pigs, or dogs, ethyl paraben is excreted in the urine as unchanged benzoate, p-hydroxybenzoic acid, p-hydroxyhippuric acid (p-hydroxybenzoylglycine), ester glucuronides, ether glucuronides, or ether sulfates.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 668
... mouse liver perfused with ethylparaben rapidly hydrolyzed it to the free acid within 60 minutes. When given orally to dogs at 25 to 500 mg/kg, no ethylparaben was detected in their blood until a dose of 500 mg/kg was reached. No ethylparaben was detected in the blood of six humans 4 hr following oral administration of 10 to 20 mg/kg. High serum concentrations of p-hydroxybenzoic acid appeared rapidly. The authors stated that ethylparaben, ingested in food by man, was probably completely hydrolyzed within 3 minutes after absorption.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 27. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
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. Recovery of butylparaben after oral administration was 40% and 48 after IV administration. The authors considered this finding a result of less effective hydrolysis of butylparaben. 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.
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 26. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
It is well known that in vitro preparations of the chick embryo can functionalize and conjugate selected model substances. Based on this biochemical knowledge an ex vivo model was developed to study xenobiotic metabolism in the incubated hen's egg. The xenobiotic is injected into the yolk sac, i.e. the nutritional compartment, on day 6 and metabolites are identified in the excretion medium of the embryonic kidneys (allantoic fluid) on day 11. During this developmental period the embryo lacks or has very limited sensitivity. Thus the model is in accordance with the 3R concept. In the present investigation ethyl 4-hydroxybenzoate was chosen as a test substance. Concentrations of this paraben up to 24 mg/egg did not affect embryo viability. After inoculation of 6 mg/egg, 4-hydroxybenzoic acid and 4,4'-dihydroxy-L-ornithuric acid were identified in their free form. The 4-hydroxybenzoic acid was also eliminated in its conjugated form (glucuronide and/or sulfate). No unchanged paraben was excreted. 4,4'-dihydroxy-L-ornithuric acid [2,5-bis-(4-hydroxybenzoylamino)pentanoic acid] is a new metabolite. The structure of this amino acid conjugate was elucidated by synthesis and spectral methods (MS, 1H and 13C NMR).
Kiep L; ALTEX 22 (3): 135-41 (2005)

4.2 Absorption, Distribution and Excretion (Complete)

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. /4-Hydroxybenzoates (Parabens)/
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 639
... Deposition of parabens in dogs. Urine recoveries ranged from 50-95% except for butyl ester for which recoveries were 40%. /It/... was concluded that esters are well absorbed and that hydrolysis of ester linkage and metabolic conjugation constitute chief route of elimination. Similar metabolic scheme ... in man. /Parabens/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 126
The permeation of methylparaben, ethylparaben, propylparaben, and butylparaben through untreated and lipid-depleted excised guinea pig dorsal skin, and the effects of 3 penetration enhancers, N-dodecyl-2-pyrrolidone (lauryl pyrrolidone), ethyl alcohol (ethanol), and a mixture of menthol (l-menthol) and ethyl alcohol, on the permeation of the parabens were studied; the relationship between the permeability and octyl alcohol (n-octanol)/water partition coefficients of the parabens, and the effect of the penetration enhancers on the fluidity of the lipid bilayer of liposomes containing stratum corneum lipids were also examined. Permeability coefficients of the parabens correlated with their octyl alcohol/water partition coefficients in untreated guinea pig skin. In lipid-depleted guinea pig skin, permeability coefficients of the parabens increased and did not correlate with their octyl alcohol/water partition coefficients. The effect of the penetration enhancers on the permeation of the parabens was variable. The penetration enhancers increased the fluidity of liposome lipid bilayers.
Kitagawa S et al; Chem Pharm Bull 45 (Aug): 1354-7 (1997)
After ethyl paraben is intravenously infused into the dog, unhydrolyzed ethyl 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 ethyl paraben (427 and 648 ug/cu cm, respectively) is reached. After 48 hr, all ethyl paraben is completely eliminated.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. V6 668

5 Pharmacology

5.1 Interactions (Complete)

The biological fates of ethyl paraben after the simultaneous administration with salicylic acid were different from those of ethyl paraben alone as reported in the previous reports. The excretion of unconjugated p-hydroxybenzoic acid, which is a hydrolyzed product of ethyl paraben, increased and those of p-hydroxyhippuric acid, glycine conjugate of p-hydroxybenzoic acid, and p-hydroxybenzoyl glucuronide, its ester type glucuronide, decreased. The blood concentration patterns were considerably different from those of ethyl paraben alone, especially the elimination of every metabolite was delayed. Pharmacokinetic analyses on the data of blood concentration were carried out and the results also show the interaction of salicylic acid on the biological fate of ethyl paraben.
Kiwada H et al; J Pharmacobiodyn 4 (8): 643-8 (1981)

6 Environmental Fate & Exposure

6.1 Environmental Fate / Exposure Summary

Ethylparaben's production and use as a preservative for pharmaceutical, cosmetic products and in food packaging may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 9.3X10-5 mm Hg at 25 °C indicates ethylparaben will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase ethylparaben will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 13 days. Particulate-phase ethylparaben will be removed from the atmosphere by wet or dry deposition. Ethylparaben contains chromophores that absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, ethylparaben is expected to have high to moderate mobility based upon Kocs ranging from 119 to 209. The pKa of ethylparaben is 8.34, indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 4.8X10-9 atm-cu m/mole. If released into water, ethylparaben is not expected to adsorb to suspended solids and sediment based upon the Koc. Biodegradation is expected to be an important environmental fate process for this compound given measured half-lives of 3.5 and 14 days in activated sludge. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 20 suggests the potential for bioconcentration in aquatic organisms is low. Ethylparaben is not expected to undergo readily hydrolysis in the environment based on estimated based-catalyzed second-order hydrolysis half-life estimations of 3.7 and 37 years at pH levels of 8 and 7, respectively. Occupational exposure may occur through dermal contact with this compound at workplaces where ethylparaben is produced or used. The general population may be exposed to ethylparaben via ingestion and dermal contact through use of cosmetic and pharmaceutical products containing this compound. (SRC)

6.2 Probable Routes of Human Exposure (Complete)

NIOSH (NOES Survey 1981-1983) has statistically estimated that 4,591 workers (1,145 of these are female) are potentially exposed to ethylparaben in the US(1). Occupational exposure to ethylparaben may occur through dermal contact with this compound at workplaces where ethylparaben is produced or used(SRC). The general population may be exposed to ethylparaben via ingestion and dermal contact through use of cosmetic and pharmaceutical products containing this compound(SRC).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available at https://www.cdc.gov/noes/ as of January 16, 2007.

6.3 Artificial Pollution Sources (Complete)

Ethylparaben's production and use as a preservative for pharmaceuticals, adhesives and cosmetics(1,2) and in food packaging(3) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 708 (2013)
(2) David RM et al; Esters of Mono-, Di-, and Tricarboxylic Acids. Patty's Toxicology. 6th ed. (1999-2016). New York, NY: John Wiley & Sons, Inc. On-line Posting Date: 17 Aug 2012
(3) CDC; Biomonitroing Summary. Parabens. Atalanta, GA: Center for Disease Control. Available from, as of Nov 3, 2016: https://www.cdc.gov/BIOMONITORING/Parabens_BiomonitoringSummary.html

6.4 Environmental Fate (Complete)

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 119 to 209(2) indicate that ethylparaben is expected to have high to moderate mobility in soil(SRC). The pKa of ethylparaben is 8.34(3), indicating that this compound will partially exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of ethylparaben from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.8X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(5). Ethylparaben is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.3X10-5 mm Hg(SRC), determined from a fragment constant method(6). Half-lives of about 14 days and 3.5 days were measured in aerobic screening tests conducted with phenol- and cresol-acclimated sludge over 7 day and 1 day incubation periods(7,8), respectively, suggesting that biodegradation may be an important fate process in soil(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Von Oepen B et al; Chemosphere 22: 258-304 (1991)
(3) Yonezawa Y et al; Kogai Shigen Kenkyusho Iho 15: 75-86 (1985)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
(5) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(6) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 3, 2016: https://www2.epa.gov/tsca-screening-tools
(7) Urushigawa Y et al; Kogai Shigen Kenkyusho Iho 12: 49-54 (1983)
(8) Urushigawa Y et al; Kogai Shigen Kenkyusho Iho 13: 59-65 (1984)
AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 119 to 209(2), indicate that ethylparaben is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.8X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 20(SRC), from its log Kow of 2.47(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Half-lives of about 14 days and 3.5 days were measured in aerobic screening tests conducted with phenol- and cresol-acclimated sludge over 7 day and 1 day incubation periods(8,9), respectively, suggesting that biodegradation may be an important fate process in water(SRC).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) Von Oepen B et al; Chemosphere 22: 258-304 (1991)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 57 (1995)
(7) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 3, 2016: https://www2.epa.gov/tsca-screening-tools
(8) Urushigawa Y et al; Kogai Shigen Kenkyusho Iho 12: 49-54 (1983)
(9) Urushigawa Y et al; Kogai Shigen Kenkyusho Iho 13: 59-65 (1984)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ethylparaben, which has an estimated vapor pressure of 9.3X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase ethylparaben is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be one day(SRC), calculated from its rate constant of 1.3X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase ethylparaben may be removed from the air by wet and dry deposition(SRC). Ethylparaben contains chromophores that absorb at wavelengths >290 nm(4) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 3, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

6.5 Environmental Biodegradation (Complete)

AEROBIC: Biodegradation is expected to be an important environmental fate process for this compound(SRC). A pseudo first-order rate constant of 2.07X10-3 hr-1 was measured in an aerobic screening test conducted with a phenol-acclimated sludge inoculum over a 7 day incubation period(1). This corresponds to a half-life of about 14 days(1). A rate constant of 8.27X10-3 hr-1 was measured in an aerobic screening test conducted with a cresol-acclimated sludge inoculum over a 1 day incubation period(2). This corresponds to a half-life of about 3.5 days(2). Average concentrations of not detected, 0.84, 0.05 and 0.85 ng/L were reported for ethylparaben in gray water from 32 residences and associated effluent from aerobic, anaerobic and anaerobic+aerobic biological treatment systems, respectively. Testing was done in August, 2008 in Sneek, The Netherlands(3). Ethylparaben, present at an average concentration of 880 ng/L, exhibited half-lives of 1.8 days and 27.5 hours using an activated sludge batch test and a real wastewater treatment plant test, respectively; sampling was conducted during April and May 2010 in a metropolitan area of northwest Spain(4).
(1) Urushigawa Y et al; Kogai Shigen Kenkyusho Iho 12: 49-54 (1983)
(2) Urushigawa Y et al; Kogai Shigen Kenkyusho Iho 13: 59-65 (1984)
(3) Hernandez Leal L et al; Environ Sci Technol 44(17): 6835-6842 (2010)
(4) Gonzalez-Marino I et al; Water Res 45(20): 6770-6780 (2011)

6.6 Environmental Abiotic Degradation (Complete)

The rate constant for the vapor-phase reaction of ethylparaben with photochemically-produced hydroxyl radicals has been estimated as 1.3X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about one day at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A base-catalyzed second-order hydrolysis rate constant of 6.0X10-3 L/mole-sec(SRC) was estimated using a structure estimation method(2); this corresponds to half-lives of 37 and 3.7 years at pH values of 7 and 8, respectively(2). Although hydrolysis of ethylparaben is possible, it is not expected to be an important fate process under environmental conditions(SRC). Ethylparaben contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 3, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

6.7 Environmental Bioconcentration (Complete)

An estimated BCF of 20 was calculated for ethylparaben(SRC), using a log Kow of 2.47(1) and a regression derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Hansch C et al; Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Prof Ref Book. Heller SR, consult. ed., Washington, DC: Amer Chem Soc p. 57 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 3, 2016: https://www2.epa.gov/tsca-screening-tools
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

6.8 Soil Adsorption / Mobility (Complete)

Koc values of 209, 162 and 119 have been reported for acidic forest soil, agricultural soil and sediment samples obtained from Lake Constance, Germany, respectively(1). Based on a recommended classification scheme(2), these Koc values indicate that ethylparaben is expected to have high to moderate mobility in soil. The pKa of ethylparaben is 8.34(3), indicating that this compound will partially exist in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
(1) Von Oepen B et al; Chemosphere 22: 258-304 (1991)
(2) Swann RL et al; Res Rev 85: 23 (1983)
(3) Yonezawa Y et al; Kogai Shigen Kenkyusho Iho 15: 75-86 (1985)
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

6.9 Volatilization from Water / Soil (Complete)

The Henry's Law constant for ethylparaben is estimated as 4.8X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that ethylparaben is expected to be essentially nonvolatile from water and moist soil surfaces(2). Ethylparaben is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.3X10-5 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)
(3) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Nov, 2012. Available from, as of Nov 3, 2016: https://www2.epa.gov/tsca-screening-tools

6.10 Environmental Water Concentrations (Complete)

DRINKING WATER: Ethylparaben was not detected in 8 of 8 drinking water samples from different cities in the Turia River Basin, Spain. The average concentration in mineral waters was 2 ng/L (2 of 2 samples positive). Sampling was conducted in October, 2012; limit of quantitation = 0.3(1).
(1) Carmona E et al; Sci Total Environ 484: 53-63 (2014)
SURFACE WATER: Ethylbaraben was detected in the Turia River, Valencia, Spain. The average concentration from 22 samples was 16 ng/L (13 samples positive). Sampling was conducted in October, 2012; limit of quantitation = 1.0(1).
(1) Carmona E et al; Sci Total Environ 484: 53-63 (2014)

6.11 Effluent Concentrations (Complete)

The average concentration of ethylparaben in 21 influent and effluent samples from wastewater treatment plants on the Turia River, Valencia, Spain were 72 ng/L (21 samples positive) and not detected (21 samples positive), respectively. Sampling was conducted in October, 2012; limit of quantitation effluent = 1.5(1). The compound was detected at a range of 589-2002, 4-50 and 1-13 ng/L in influent, final effluent and surface waters, respectively, in the UK(2).
(1) Carmona E et al; Sci Total Environ 484: 53-63 (2014)
(2) Petrie B et al; Water Res 72: 3-27 (2015)

6.12 Sediment / Soil Concentrations (Complete)

SEDIMENT: The average concentration of ethylparaben from 22 sediment samples from the Turia River, Valencia, Spain was 23 ng/g (19 samples positive). Sampling was conducted in October, 2012; limit of quantitation = 2.6(1).
(1) Carmona E et al; Sci Total Environ 484: 53-63 (2014)

6.13 Food Survey Values (Complete)

Occurrence of ethylparaben in food samples collected from several grocery stores in Albany, NY in 2008, 2011 and 2012(1).
Commodity
Beverages
No. Samples
33
Mean (ng/g)
8.53
% Frequency
12.1
Commodity
Dairy products
No. Samples
31
Mean (ng/g)
0.160
% Frequency
48.4
Commodity
Fats and oils
No. Samples
5
Mean (ng/g)
0.031
% Frequency
40.0
Commodity
Fish and shellfish
No. Samples
23
Mean (ng/g)
0.111
% Frequency
56.5
Commodity
Grains
No. Samples
54
Mean (ng/g)
3.17
% Frequency
66.7
Commodity
Meat
No. Samples
52
Mean (ng/g)
0.100
% Frequency
73.1
Commodity
Fruits
No. Samples
20
Mean (ng/g)
0.182
% Frequency
55.0
Commodity
Vegetables
No. Samples
49
Mean (ng/g)
2.74
% Frequency
73.5
(1) Liao C et al; Environ Sci Technol 47: 3918-25 (2013)

6.14 Fish / Seafood Concentrations (Complete)

Ethylparaben was reported at a mean concentration of 0.111 ng/g (range of not detected to 2.27 ng/g) in fish and shellfish samples collected from several grocery stores in Albany, NY in 2008, 2011 and 2012; 23 samples, 56.5% detection frequency(1).
(1) Liao C et al; Environ Sci Technol 47: 3918-25 (2013)

6.15 Other Environmental Concentrations (Complete)

Ethylparaben concentrations in 158 indoor dust samples (13 cities, 4 countries) from the United States, China, Korea and Japan(1).
Country
USA
No Samples
40
Median concn (ng/g)
33
Range (ng/g)
<LOQ to 679
Detection Rate (%)
94.7
Country
China
No Samples
55
Median concn (ng/g)
11
Range (ng/g)
<LOQ to 2410
Detection Rate (%)
90.9
Country
Korea
No Samples
41
Median concn (ng/g)
46
Range (ng/g)
2.9-560
Detection Rate (%)
100
Country
Japan
No Samples
22
Median concn (ng/g)
127
Range (ng/g)
<LOQ to 3110
Detection Rate (%)
95.5
(1) Wang L et al; Environ Sci Technol 46: 11584-93 (2012)

7 Environmental Standards & Regulations

7.1 FDA Requirements (Complete)

Ethyl p-hydroxybenzoate is an indirect food additive for use only as a component of adhesives.
21 CFR 175.105 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of October 21, 2016: https://www.ecfr.gov

8 Chemical / Physical Properties

8.1 Molecular Formula

C9-H10-O3
ChemID

8.2 Molecular Weight

166.173
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-260

8.3 Color / Form (Complete)

Small, colorless crystals or powder at room temperature
David RM et al; Esters of Mono-, Di-, and Tricarboxylic Acids. Patty's Toxicology. 6th ed. (1999-2016). New York, NY: John Wiley & Sons, Inc. On-line Posting Date: 17 Aug 2012
Crystals from dilute alcohol
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-260

8.4 Odor

Odorless
David RM et al; Esters of Mono-, Di-, and Tricarboxylic Acids. Patty's Toxicology. 6th ed. (1999-2016). New York, NY: John Wiley & Sons, Inc. On-line Posting Date: 17 Aug 2012

8.5 Boiling Point

297-298 °C (decomposition)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 708

8.6 Melting Point

117 °C
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-260

8.7 LogP

log Kow = 2.47
Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 57

8.8 Dissociation Constants

pKa = 8.34
Yonezawa Y et al; Kogai Shigen Kenkyusho Iho 15: 75-86 (1985)

8.9 Solubility (Complete)

In water, 8.85X10+2 mg/L at 25 °C
Yalkowsky, S.H., He, Yan, Jain, P. Handbook of Aqueous Solubility Data Second Edition. CRC Press, Boca Raton, FL 2010, p. 583
Solubility in water at 25 °C is 0.075% w/w; at 20 °C. 0.70% w/w
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 708
Solubilities in various solvents
Solvent
Methanol
g/100g at 25 °C
115
Solvent
Ethanol
g/100g at 25 °C
70
Solvent
Propylene glycol
g/100g at 25 °C
25
Solvent
Peanut oil
g/100g at 25 °C
1
Solvent
Acetone
g/100g at 25 °C
84
Solvent
Benzene
g/100g at 25 °C
1.65
Solvent
Ether
g/100g at 25 °C
43
Solvent
Carbon tetrachloride
g/100g at 25 °C
0.9
Thomas MR; Salicylic Acid and Related Compounds. Ullmann's Encyclopedia of Industrial Chemistry. 7th ed. (1999-2016). New York, NY: John Wiley & Sons. Online Posting Date: 26 Jan 2006.
AT 25 °C: 0.5 G/100 G GLYCERIN
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 123
Slightly soluble in chloroform, trifluoroacetic acid; very soluble in ethanol, ethyl ether; insoluble in carbon disulfide
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-260
Freely soluble in alcohol, ether, acetone, propylene glycol; slightly soluble in glycerin
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 708

8.10 Other Experimental Properties (Complete)

ODORLESS /ESTERS OF PARA-HYDROXYBENZOIC ACID/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 1095

9 Spectral Information

9.1 1D NMR Spectra

1D NMR Spectra
1H NMR: 1192 (Sadtler Research Laboratories Spectral Collection)

9.2 Mass Spectrometry

9.2.1 Other MS

Other MS
MASS: 6292 (NIST/EPA/MCDC Mass Spectral Database 1990 version); 907 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)

9.3 UV Spectra

UV: 970 (Sadtler Research Laboratories Spectral Collection)
Lide, D.R., G.W.A. Milne (eds.). Handbook of Data on Organic Compounds. Volume I. 3rd ed. CRC Press, Inc. Boca Raton ,FL. 1994., p. V2: 1452

9.4 IR Spectra

IR Spectra
IR: 370 (Sadtler Research Laboratories IR Grating Collection)

9.5 Other Spectra

SADTLER REF NUMBER: 3250 (IR, PRISM)
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 57th ed. Cleveland: CRC Press Inc., 1976., p. C-193
Intense mass spectral peaks: 121 m/z, 138 m/z, 166 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 229

10 Chemical Safety & Handling

10.1 GHS Classification

GHS Hazard Statements
H401: Toxic to aquatic life [Hazardous to the aquatic environment, acute hazard]
Precautionary Statement Codes

P273, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

10.2 Fire Fighting Procedures (Complete)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html

10.3 Hazardous Reactivities and Incompatibilities (Complete)

Incompatible materials: Strong oxidizing agents, strong bases
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html

10.4 Personal Protective Equipment (PPE) (Complete)

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html

10.5 Preventive Measures (Complete)

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Precautions for safe handling: Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

10.6 Stability / Shelf Life (Complete)

Stable under recommended storage conditions.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html
Parabens are stable against hydrolysis during autoclaving & resist saponification /Parabens/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 124
Calcium salts /are/ stable; sodium salts /are/ unstable. /Parabens/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 124

10.7 Storage Conditions (Complete)

Keep container tightly closed in a dry and well-ventilated place.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html

10.8 Cleanup Methods (Complete)

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html

10.9 Disposal Methods (Complete)

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Safety Data Sheet for Ethyl 4-hydroxybenzoate. Product Number: 111988, Version 3.7 (Revision Date 06/28/2014). Available from, as of October 7, 2016: https://www.sigmaaldrich.com/safety-center.html

11 Manufacturing / Use Information

11.1 Uses (Complete)

For ethylparaben (USEPA/OPP Pesticide Code: 061202) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
National Pesticide Information Retrieval System's Database on Ethylparaben (120-47-8). Available from, as of October 24, 2016: https://npirspublic.ceris.purdue.edu/ppis/
Antimicrobial preservative for pharmaceuticals.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 708
Ethyl paraben ... inhibits the growth of fungi and bacteria and is used as a preservative for pharmaceuticals, adhesives, and various cosmetic preparations.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:667
... Antibacterials that prevent /food spoilage by/ Clostridium botulinum include ... parabens ... /Parabens/
Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 1081

11.2 Manufacturers

Sigma-Aldrich, 3050 Spruce St., Saint Louis, MO 63103, (800) 325-5832
Sigma-Aldrich; Product Search Ethyl paraben (12-047-8). Available from, as of Nov 1, 2016: https://www.sigmaaldrich.com/united-states.html
Penta Manufacturing Co., 80 Okner Pkwy., Livingston, NJ 07039-1604, (973) 740-2300; Production site: Livingston, NJ 07039-1604
SRI Consulting. 2011 Directory of Chemical Producers United States. SRI Consulting, Menlo Park, CA 2011, p. 644

11.3 Methods of Manufacturing (Complete)

Prepared by esterification of p-hydroxybenzoic acid.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 708
Parabens are prepared by esterifying PHBA /parahydroxybenzoic acid/ with the corresponding alcohol in the presence of an acid catalyst, such as sulfuric acid, and an excess of the specific alcohol. The acid is then neutralized with caustic soda, and the product is crystallized by cooling, centrifuged, washed, dried under vacuum, milled, and blended. /Parabens/
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 2. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf

11.4 General Manufacturing Information (Complete)

The parabens are most active against molds and yeasts. They are less effective against bacteria, especially gram-negative bacteria. /Parabens/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 125

11.5 Formulations / Preparations (Complete)

Trade Names: Aseptoform E, Bobomold OE, Easeptol, Ethyl butex, Ethyl parasept, Mycoten, Napagin A, Nipagina A, Nipazin A, Sobrol A, Solbrol A, and Tegosept E.
Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 6:667

11.6 U.S. Production (Complete)

(1972) PROBABLY GREATER THAN 9.08X10+5 GRAMS
SRI
(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS
SRI
Production volumes for non-confidential chemicals reported under the Inventory Update Rule.
Year
1986
Production Range (pounds)
10 thousand - 500 thousand
Year
1990
Production Range (pounds)
10 thousand - 500 thousand
Year
1994
Production Range (pounds)
No Reports
Year
1998
Production Range (pounds)
No Reports
Year
2002
Production Range (pounds)
10 thousand - 500 thousand
US EPA; Non-confidential Production Volume Information Submitted by Companies for Chemicals Under the 1986-2002 Inventory Update Rule (IUR). Benzoic acid, 4-hydroxy-, ethyl ester (120-47-8). Available from, as of March 6, 2007: https://www.epa.gov/oppt/iur/tools/data/2002-vol.html

12 Laboratory Methods

12.1 Clinical Laboratory Methods (Complete)

Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ng/mL, respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ng/mL, respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones.
Jimenez-Diaz I et al; Sci Total Environ 562: 81-8 (2016)
Parabens are the most widely used preservative and are considered to be relatively safe compounds. However, studies have demonstrated that they may have estrogenic activity, and there is ongoing debate regarding the safety and potential cancer risk of using products containing these compounds. In the present work, liquid chromatography-tandem mass spectrometry was applied to determine methylparaben and propylparaben concentrations in serum, and the results were correlated with lipstick application. Samples were analyzed using liquid-liquid extraction, followed by liquid chromatography-tandem mass spectrometry. The validation results demonstrated the linearity of the method over a range of 1-20 ng/mL, in addition to the method's precision and accuracy. A statistically significant difference was demonstrated between serum parabens in women who used lipstick containing these substances compared with those not using this cosmetic (p = 0.0005 and 0.0016, respectively), and a strong association was observed between serum parabens and lipstick use (Spearman correlation = 0.7202).
Tahan GP et al; Regul Toxicol Pharmacol 79: 42-8 (2016)

12.2 Analytic Laboratory Methods (Complete)

By combining chromatographic methods with spectrophotometry /it is possible/ ... to separate and quantitatively determine sorbic acid, benzoic acid and methyl, ethyl, propyl and butyl esters of p-hydroxybenzoic acid. /Parabens/
Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 129
Determinations of parabens in aqueous solutions by gas-liquid chromatography.
Hopp E; Medd Nor Farm Selsk 40(3) 153-7 (1978)
Chromatography, especially high-pressure liquid chromatography, is used presently for determination of parabens in foods, cosmetics, and pharmaceuticals. Parabens may be determined directly, or they may be chemically modified and the derivative subsequently identified. /Parabens/
Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products p 3. Int J Toxicol 27 Suppl 4: 1-82 (2008). Available from, as of November 21, 2016: https://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf
Parabens are widely used in ... cosmetics and personal care products. Thus, in this work a multi-syringe chromatographic (MSC) system is proposed for the first time for the determination of four parabens: methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) in cosmetics and personal care products, as a simpler, practical, and low cost alternative to HPLC methods. Separation was achieved using a 5 mm-long precolumn of reversed phase C18 and multi-isocratic separation, i.e. using two consecutive mobile phases, 12:88 acetonitrile:water and 28:72 acetonitrile:water. The use of a multi-syringe buret allowed the easy implementation of chemiluminescent (CL) detection after separation. The chemiluminescent detection is based on the reduction of Ce(IV) by p-hydroxybenzoic acid, product of the acid hydrolysis of parabens, to excite rhodamine 6G (Rho 6G) and measure the resulting light emission. Multivariate designs combined with the concepts of multiple response treatments and desirability functions have been employed to simultaneously optimize and evaluate the responses. The optimized method has proved to be sensitive and precise, obtaining limits of detection between 20 and 40 ug L(-1) and RSD <4.9% in all cases. The method was satisfactorily applied to cosmetics and personal care products, obtaining no significant differences at a confidence level of 95% comparing with the HPLC reference method.
Rodas M et al; Talanta 143: 254-62 (2015)

13 Special References

13.1 Special Reports (Complete)

Cosmetic Ingredient Review; Final Amended Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in Cosmetic Products. Int J Toxicol 27 Suppl 4: 1-82 (2008)[Available from, as of November 21, 2016: http://online.personalcarecouncil.org/ctfa-static/online/lists/cir-pdfs/PR427.pdf]

14 Synonyms and Identifiers

Synonyms

120-47-8

ETHYLPARABEN

Benzoic acid, 4-hydroxy-, ethyl ester

Benzoic acid, p-hydroxy-, ethyl ester

Carbethoxyphenol

p-Carbethoxyphenol

Pesticide Code: 061202

Ethylester kyseliny p-hydroxybenzoove (Czech)

Ethyl p-hydroxybenzoate

p-Hydroxybenzoate ethyl ester

p-Hydroxybenzoic acid ethyl ester

4-Hydroxybenzoic acid ethyl ester

p-Hydroxybenzoic ethyl ester

p-Oxybenzoesaeureaethylester (German)

UNII-14255EXE39

Ethyl 4-Hydroxybenzoate

14.2 Substance Title

ETHYLPARABEN

15 Administrative Information

15.1 Hazardous Substances DataBank Number

938

15.2 Last Revision Date

20170228

15.3 Last Review Date

Reviewed by SRP on 1/12/2017

15.4 Update History

Complete Update on 2017-02-28, 51 fields added/edited/deleted

Complete Update on 2007-10-11, 35 fields added/edited/deleted

Complete Update on 03/26/2003, 36 fields added/edited/deleted.

Field Update on 02/14/2003, 1 field added/edited/deleted.

Field Update on 11/08/2002, 1 field added/edited/deleted.

Field Update on 08/06/2002, 1 field added/edited/deleted.

Field Update on 01/14/2002, 1 field added/edited/deleted.

Field Update on 08/08/2001, 1 field added/edited/deleted.

Field Update on 05/15/2001, 1 field added/edited/deleted.

Field Update on 06/12/2000, 1 field added/edited/deleted.

Field Update on 06/12/2000, 1 field added/edited/deleted.

Field Update on 02/08/2000, 1 field added/edited/deleted.

Field Update on 02/02/2000, 1 field added/edited/deleted.

Field Update on 11/18/1999, 1 field added/edited/deleted.

Field Update on 09/21/1999, 1 field added/edited/deleted.

Field Update on 08/26/1999, 1 field added/edited/deleted.

Field Update on 06/02/1998, 1 field added/edited/deleted.

Field Update on 02/27/1998, 1 field added/edited/deleted.

Field Update on 10/20/1997, 1 field added/edited/deleted.

Complete Update on 01/24/1997, 1 field added/edited/deleted.

Complete Update on 05/10/1996, 1 field added/edited/deleted.

Complete Update on 01/19/1996, 1 field added/edited/deleted.

Complete Update on 12/22/1994, 1 field added/edited/deleted.

Complete Update on 08/18/1994, 1 field added/edited/deleted.

Complete Update on 03/25/1994, 1 field added/edited/deleted.

Complete Update on 04/28/1993, 1 field added/edited/deleted.

Field update on 12/16/1992, 1 field added/edited/deleted.

Complete Update on 10/22/1990, 1 field added/edited/deleted.

Complete Update on 04/16/1990, 1 field added/edited/deleted.

Field update on 03/06/1990, 1 field added/edited/deleted.

Complete Update on 12/20/1984

Created 19830401 by SYS

CONTENTS