Parabens are the most commonly used preservatives in cosmetic, pharmaceutical, and industrial products. The epidemiology, structural properties, allergenicity, hormonal properties, and hypotheses regarding the “paraben paradox” are addressed in this review.
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References
1.
RichardsonEL.Up-date frequency of preservative use in cosmetic formulas as disclosed to FDA. Cosmetic and Toiletries FDA Report, 1977; 92:85.
MaddoxDN.The role of p-hydroxybenzoates in modern cosmetics. Cosmetic Toiletries, FDA Report, 1982; 97:85-8.
4.
FukahoriM, AkatsuS, SatoH, YotsuyanagiT. Relationship between uptake of p-hydroxybenzoic acid esters by Escherichia coli and antibacterial activity. Chem Pharm Bull Tokyo, 1996; 44:1567-70.
5.
KangSH, KimH. Simultaneous determination of methylparaben, propylparaben and thimerosal by high-performance liquid chromatography and electrochemical detection. J Pharm Biomed Anal, 1997; 15:1359-63.
6.
FisherAA.Esoteric contact dermatitis. Part 1: The paraben paradox. Cutis, 1996; 57:65-6.
7.
LorenzettiOJ, WernetTC. Topical parabens: benefits and risks. Dermatologica, 1977; 154:244-50.
8.
SassevilleD.Hypersensitivity to preservatives. Dermatol Ther, 2004; 17:251-63.
9.
RastogiSC, SchoutenA, KruijFN, WeijlandJW. Contents of methyl-, ethyl-, propyl-, butyl- and benzylparaben in cosmetic products. Contact Dermatitis, 1995; 32:28-30.
10.
ElderRL.Final report on the safety assessment of methylparaben, ethylparaben, propylparaben and butylparaben. J Am Coll Toxicol, 1984; 3:147-209.
11.
MowadCM.Allergic contact dermatitis caused by parabens: two case reports and a review. Am J Contact Dermat, 2000; 11:53-5.
12.
FranswayAF.The problems of preservation in the 1990s. II. Agents with preservative function independent of formaldehyde release. Am J Contact Dermat, 1991; 2:145-74.
13.
BergfeldW, BelsitoD, MarksJJr, AndersenF. Safety of ingredients used in cosmetics. J Am Acad Dermatol, 2005; 52:125-32.
14.
OishiS.Lack of spermatotoxic effects of methyl and ethyl esters of p-hydroxybenzoic acid in rats. Food Chem Toxicol, 2004; 42: 1845-9.
15.
TwistJN, ZatsJL. Influence of solvents on parabens permeation through idealized skin model membranes. J Soc Cosmet Chem, 1986; 37:429-44.
16.
LeeCH, KimHJ. A study on the absorption mechanisms of drug through membranes. Arch Pharm Res, 1994; 17:182-9.
17.
SoniMG, BurdockGA, TaylorSL, GreenbergNA. Safety assessment of propyl paraben: a review of the published literature. Food Chem Toxicol, 2001; 39:513-2.
18.
RietschelRL, FowlerJFJr. Dermatitis to preservatives and other additives in cosmetics and medications. In: RietschelRL, FowlerJFJr, editors. Fisher's contact dermatitis. 4th ed. Philadelphia: Williams & Wilkins; 1995. p. 266-7.
19.
SoniMG, TaylorSL, GreenbergNA, BurdockGA. Evaluation of the health aspects of methyl paraben: a review of the published literature. Food Chem Toxicol, 2002; 40:1335-73.
20.
SchubertH, BaumbachN, PraterE, et al.Patch testing with parabens. Contact Dermatitis, 1990; 23:245-6.
21.
KomatsuH.Percutaneous absorption of butyl paraben in vitro. II. Effects of micellar trapping of drug and percutaneous absorption of nonionic surfactants. Chem Pharm Bull, 1984; 32: 3739-43.
22.
EspositoE, BortolottiF, NastruzziC, et al.Diffusion of preservatives from topical dosage forms: a comparative study. J Cosmet Sci, 2003; 54:239-50.
23.
HanJ, WashingtonC. Partition of antimicrobial additives in an intravenous emulsion and their effect on emulsion physical stability. Int J Pharm, 2005; 288:263-71.
24.
LobemeierC, TschoetschelC, WestieS, HeymannE. Hydrolysis of parabens by extracts from differing layers of human skin. Biol Chem, 1996; 377:647-51.
25.
NakazawaH, OdaH, FujisimaH, et al.[Analysis of chlorobenzenes, para-hydroxybenzoic acid esters and herbicide in human subjects using GC/MS.] A report of the Research Fund of Health and Welfare of Japan. Tokyo: Ministry of Health and Welfare of Japan; 1999. p. 16.
26.
RietschelRL, FowlerJFJr. Allergy to preservatives and vehicles in cosmetics and toiletries. In: RietschelRL, FowlerJFJr, editors. Fisher's contact dermatitis. 5th ed. Philadelphia: Lippincott, Williams & Wilkins; 2001. p. 211-59.
27.
SokoloskiWT, ChidesterCG, HoneywellGE. The hydrolysis of methyl p-hydroxybenzoate by Cladosporium resinae. Dev Ind Microbiol, 1962; 3:179-87.
28.
HugoWB, FosterJHS. Growth of Pseudomonas aeruginosa in solutions of esters of p-hydroxybenzoic acid. J Pharm Pharmacol, 1964; 16:209.
29.
CloseJA, NeilsenPA. Resistance of a strain of Pseudomonas cepacia to esters of p-hydroxybenzoic acid. Appl Environ Microbiol, 1976; 31:718-22.
ValkovaN, LepineF, LabrioL, et al.Purification and characterization of PrbA, a new esterase from Enterobacter cloacae hydrolyzing the esters of 4-hydroxybenzoic acid (parabens). J Biol Chem, 2003; 278:12779-85.
32.
KokRG, D'ArgenioDA, OrnstonLN. Mutation analysis of PobR and PcaU, closely related transcription activation in Acinetobacter. J Bacteriol, 1998; 180:5058-69.
33.
HutchinsonJ, RungeW, MulveyM, et al.Burkholderia cepacia infections associated with intrinsically contaminated ultrasound gel: the role of microbial degradation of parabens. Infect Control Hosp Epidemiol, 2004; 25:291-6.
34.
ValkovaN, LepineF, ValeanuL, et al.Hydrolysis of 4-hydroxybenzoic acid esters (parabens) and their aerobic transformation into phenol by the resistant Enterobacter cloacae strain EM. Appl Environ Microbiol, 2001; 67:2404-9.
35.
ValkovaN, LepineF, BolletC, et al.PrbA, a gene coding for an esterase hydrolyzing parabens in Enterobacter cloacae and Enterobacter gergoviae strains. J Bacteriol, 2002; 184:5011-7.
36.
TresoldiAT, PadovezeMC, TrabassoP, et al.Enterobacter cloacae sepsis outbreak in a newborn unit caused by contaminated total parenteral nutrition solution. Am J Infect Control, 2000; 28:258-61.
37.
ArchibaldLK, RamosM, ArduinoMJ, et al.Enterobacter cloacae and Pseudomonas aerugnosa polymicrobial bloodstream infections traced to extrinsic contamination of a dextrose multidose vial. J Pediatr, 1998; 133:640-4.
38.
WangSA, LevineRB, CarsonLA, et al.An outbreak of gram-negative bacteremia in hemodialysis patients traced to hemodialysis machine waste drain ports. Infect Control Hosp Epidemiol, 1999; 20:746-51.
39.
BonnevieP.Overfolsomhed for aetylparauxybenzoat (Mycocten). Nord Med, 1940; 6:684-6.
KrobHA, FleischerABJr, D'AgostinoRJr, et al. Prevalence and relevance of contact dermatitis allergens: a meta-analysis of 15 years of published T.R.U.E. test data. J Am Acad Dermatol, 2004; 51:349-53.
42.
FregertS, HjorthN, MagnussonB, et al.Epidemiology of contact dermatitis. Trans St Johns Hosp Derm Soc, 1969; 55:17-35.
43.
BandmannHJ, CroninE, HjorthN, et al.Dermatitis from applied medicaments. Arch Dermatol, 1972; 106:335-7.
44.
BurryJN, KirkJ, ReidJG, et al.Environmental dermatitis: patch tests in 1,000 cases of allergic contact dermatitis. Med J Aust, 1973; 2:681-5.
45.
MarsulliFN, MaibachHI. Status of topical parabens: skin hyper sensitivity. Int J Dermatol, 1974; 13:397-9.
46.
BrunR.Epidemiology of contact dermatitis in Geneva (1000 cases). Contact Dermatitis, 1975; 1:214-7.
47.
RudnerEJ, ClendenningWE, EpsteinE, et al.The frequency of contact sensitivity in North America 1972. Contact Dermatitis, 1975; 1:277-80.
48.
RudnerEJ.North American Group results. Contact Dermatitis, 1977; 3:208-9.
49.
LepineEM.Results of routine office patch testing. Contact Dermatitis, 1976; 2:89-91.
50.
HusainSL.Contact dermatitis in the west of Scotland. Contact Dermatitis, 1977; 3:327-32.
51.
CamarasaJNG.First epidemiological study of contact dermatitis in Spain—1977. Acta Derm Venereol Suppl (Stockh), 1979; 5933-7.
52.
CalasE, CastelainPY, PiriouA. Epidemiologie des dermatoses de contact a Marseille. Ann Dermatol Venereol, 1978; 105:345-7.
LyndeCW, WarshawskiL, MitchellJC. Screening patch tests in 4190 eczema patients 1972-1981. NACDG patch test results for 1979-1980. Contact Dermatitis, 1982; 8:417-21.
55.
RomagueraC, GrimaltF. Statistical and comparative study of 4600 patients tested in Barcelona (1973-1977). Contact Dermatitis, 1980; 6:309-15.
56.
EdmanB, MollerH. Trends and forecasts for standard allergens in a 12-year patch test material. Contact Dermatitis, 1982; 8:95-104.
57.
de GrootAC, WeylandJW, BosJD, JagtmanBA. Contact allergy to preservatives (I). Contact Dermatitis, 1986; 14:120-2.
58.
de GrootAC, BosJD, JagtmanBA, et al.Contact allergy to preservatives-II. Contact Dermatitis, 1986; 15:218-22.
59.
VesteyJP, GawkrodgerDJ, WongWK, et al.An analysis of 501 consecutive contact clinic consultations. Contact Dermatitis, 1986; 15:119-25.
60.
BroeckxW, BlondeelA, Dooms-GoosensA, et al.Cosmetic intolerance. Contact Dermatitis, 1987; 16:189-94.
61.
GollhausenR, EndersF, PrzybillaB, et al.Trends in allergic contact sensitization. Contact Dermatitis, 1988; 18:147-54.
62.
HoganDJ, HillM, LanePR. Results of routine patch testing of 542 patients in Saskatoon, Canada. Contact Dermatitis, 1988; 19:120-4.
63.
EndersF, PrzybillaB, RingJ, GollhausenR. Patch test results in 1987 compared to trends from the period 1977-1983. Contact Dermatitis, 1989; 20:230-2.
64.
MacfarlaneAW, CurleyRK, GrahamRM, et al.Sensitivity to various ingredients of topical preparations following prolonged use. Contact Dermatitis, 1990; 23:367-8.
65.
GeorgeMD, SrinivasCR, BalachandranC, et al.Sensitivity to various ingredients of topical preparations following prolonged use. Contact Dermatitis, 1990; 23:367-8.
66.
SeidenariS, ManziniBM, DaneseP, et al.Patch and prick test study of 593 healthy subjects. Contact Dermatitis, 1990; 23:162-7.
67.
ShehadeSA, BeckMH, MillierVF. Epidemiological survey of standard series patch test results and observations on day 2 and day 4 readings. Contact Dermatitis, 1991; 24:119-22.
68.
MarksJG Jr, DeLeoVA. Standard allergens. In: MarksJG, DeLeoVA, editors. Contact and occupational dermatology. Philadelphia: Mosby; 1997. p. 115-7.
69.
PerrenoudD, BricherA, HunzikerT, et al.Frequency of sensitization to 13 common preservatives in Switzerland. Swiss Contact Dermatitis Research Group. Contact Dermatitis, 1994; 30:276-9.
70.
MarksJG, BelsitoDV, DeleoVA, et al.North American Contact Dermatitis Group patch test results for the detection of delayed hypersensitivity to topical allergens. J Am Acad Dermatol, 1998; 38:911-8.
71.
SchnuchA, GeierJ, UterW, FroschPJ. Patch testing with preservatives, antimicrobials and industrial biocides. Results from a multicentre study. Br J Dermatol, 1998; 138:467-76.
72.
LestringantGG, BenerA, SawayaM, et al.Allergic contact dermatitis in the United Arab Emirates. Int J Dermatol, 1999; 38:181-6.
73.
MarksJG Jr, BelsitoDV, DeLeoVA, et al.North American Contact Dermatitis Group patch-test results, 1996-1998. Arch Dermatol, 2000; 136:272-3.
74.
MarksJG Jr, BelsitoDV, DeLeoVA, et al.North American Contact Dermatitis Group patch-test results, 1998-2000. Am J Contact Dermat, 2003; 14:59-62.
75.
PrattMD, BelsitoDV, DeLeoVA, et al.North American Contact Dermatitis Group patch-test results, 2000-2002 study period. Dermatitis, 2004; 15(4):1-8.
76.
ScanbergIL.Allergic contact dermatitis to methyl and propyl paraben. Arch Dermatol, 1967; 95:626-8.
SchorrWF.Paraben allergy: a cause of intractable dermatitis. JAMA, 1968; 204:859-62.
79.
DownsAM, SansomJE, SimmonsI. Let Rip: fun pot dermatitis. Contact Dermatitis, 1998; 38:234.
80.
SimpsonJR.Dermatitis due to parabens in cosmetic creams. Contact Dermatitis, 1978; 5:311-2.
81.
VerhaegheI, Dooms-GoossensA. Multiple sources of allergic contact dermatitis from parabens. Contact Dermatitis, 1997; 36:269-70.
82.
EguinoP, SanchezA, AgestaN, et al.Allergic contact dermatitis due to propylene glycol and parabens in an ultrasonic gel. Contact Dermatitis, 2003; 48:290.
83.
PraditsuwanP, TaylorJS, RoenigkHHJr. Allergy to Unna boots in four patients. J Am Acad Dermatol, 1995; 33:906-8.
84.
FisherAA.Paraben dermatitis due to a new medicated bandage: the “paraben paradox.”. Contact Dermatitis, 1979; 5:273-4.
85.
FisherAA.Allergic paraben and benzyl alcohol hypersensitivity relationship of the “delayed” and “immediate” varieties. Contact Dermatitis, 1975; 1:281-4.
86.
FisherAA.Dermatitis of the hands from food additives. Cutis, 1982; 30:304,308,312,318,414.
87.
FotiC, BonamonteD, AntelmiA, et al.Allergic contact dermatitis to condoms: description of a clinical case and analytical review of current literature. Immunopharmacol Immunotoxicol, 2004; 26:481-5.
88.
WilkinsonJD, ShawS, AndersenKE, et al.Monitoring levels of preservative sensitivity in Europe. A 10-year overview (1991-2000). Contact Dermatitis, 2002; 46:207-10.
89.
DavisKA, GuentherL, WexlerDM. Paraben sensitivity. Can J Dermatol, 1992; 4:198-201.
90.
MachetL, CouheC, PerrinaudA, et al.A high prevalence of sensitization still persists in leg ulcer patients: a retrospective series of 106 patients tested between 2001 and 2002 and a meta-analysis of 1975-2003 data. Br J Dermatol, 2004; 150:929.
RietschelRL, FowlerJFJr. Contact urticaria. In: RietschelRL, FowlerJFJr, editors. Fisher's contact dermatitis. 4th ed. Philadelphia: Williams & Wilkins; 1995. p. 792.
101.
KajimotoY, RosenbergME, KyttaJ, et al.Anaphylactoid skin reactions after intravenous regional anaesthesia using 0.5% prilocaine with or without preservative—a double-blind study. Acta Anaesthesiol Scand, 1995; 39:782-4.
102.
AldreteJA, JohnsonDA. Allergy to local anesthetics. JAMA, 1969; 20:356-7.
103.
LatronicaRJ, GoldbergAF, WightmanJR. Local anesthetic sensitivity: report of a case. Oral Surg, 1969; 28:439-41.
FinePG, DingmanDL. Hypersensitivity dermatitis following suction-assisted lipectomy: a complication of local anesthetic. Ann Plast Surg, 1988; 20:573-5.
106.
JohnsonWT, DeStigterT. Hypersensitivity to procaine, tetracaine, mepivacaine, and methyl paraben: report of a case. J Am Dent Assoc, 1983; 106:53-6.
107.
LuebkeNH, WalkerJA. Discussion of sensitivity to preservatives in anesthetics. J Am Dent Assoc, 1978; 97:656-7.
108.
SwansonJG.Assessment of allergy to local anesthetic. Ann Emerg Med, 1983; 12:316-8.
109.
CarradoriS, PelusoAM, FaccioliM. Systemic contact dermatitis due to parabens. Contact Dermatitis, 1990; 22:238-9.
SatoK, KazamaJJ, WadaY, et al.Hypersensitivity to paraoxybenzoic acid esters (parabens) in a dialysis patient. Nephron, 2002; 92:728-9.
112.
BucksDA, McMasterJR, MaibachHI, GuyRH. Bioavailability of topically administered steroids: a “mass balance” technique. J Invest Dermatol, 1988; 91:29-33.
113.
HjorthN, Trolle-LassenC. Skin reactions to ointment bases. Trans St Johns Hosp Dermatol Soc, 1963; 49:127-40.
114.
QiaoGL, RiviereJE. Significant effects of application site and occlusion on the pharmacokinetics of cutaneous penetration and biotransformation of parathion in-vivo in swine. J Pharm Sci, 1995; 84:425-32.
115.
PottsRO.Stratum corneum hydration: experimental techniques and interpretation of results. J Soc Cosmet Chem, 1986; 37: 9-33.
116.
CrossSE, RobertsMS. The effect of occlusion on epidermal penetration of parabens from a commercial allergy test ointment, acetone and ethanol vehicles. Soc Investig Dermatol, 2000; 115: 914-8.
117.
RudzkiE, KleniewskaD. The epidemiology of contact dermatitis in Poland. Br J Dermatol, 1970; 83:543.
118.
RoutledgeEJ, ParkerJ, OdumJ, et al.Some alkyl hydroxyl benzoate preservatives (parabens) are estrogenic. Toxicol Appl Pharmacol, 1998; 153:12-9.
119.
LeminiC, SilvaG, TimossiC, et al.Estrogenic effects of p-hydroxybenzoic acid in CD1 mice. Environ Res, 1997; 75:130-4.
120.
BlairRM, FangH, BranhamWS, et al.The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci, 2000; 54:138-53.
121.
HossainiA, LarsenJJ, LarsenJC. Lack of oestrogenic effects of food preservatives (parabens) in uterotrophic assays. Food Chem Toxicol, 2000; 38:319-23.
122.
PedersenKL, PedersenSN, ChristiansenLB, et al.The preservatives ethyl-, propyl-, and butyl- paraben are estrogenic in an in vivo fish assay. Pharmacol Toxicol, 2000; 86:110-3.
123.
OkuboT, YokoyamaY, KanoK, KanoI. ER-dependent estrogenic activity of parabens assessed by proliferation of human breast cancer MCF-7 cells and expression of ERalpha and PR. Food Chem Toxicol, 2001; 39:1225-32.
124.
InuiM, AdachiT, TakenakaS, et al.Effect of UV screens and preservatives on vitellogenin and choriogenin production in male medaka (Oryzias latipes). Toxicology, 2003; 194:43-50.
125.
DarbrePO, ByfordJR, ShawLE, et al.Oestrogenic activity of benzyl paraben. J Appl Toxicol, 2003; 23:43-51.
126.
DarbrePD.Underarm cosmetics and breast cancer. J Appl Toxicol, 2003; 23:89-95.
127.
DarbrePD, AljarrahA, MillerWR, et al.Concentrations of parabens in human breast tumours. J Appl Toxicol, 2004; 24:5-13.
128.
OishiS.Effects of butyl paraben on male reproductive system in rats. Toxicol Ind Health, 2001; 17:31-9.
129.
OishiS.Effects of butyl paraben on the male reproductive system in mice. Arch Toxicol, 2002; 76:423-9.
