2-Phenoxyethanol

Preservative in DTaP, Hepatitis A, Lyme disease and Polio vaccines

Uses: a fixative for perfumes, a bactericide (in conjuction with quaternary ammoniumm compounds), an insect in germicides, in pharmaceuticals, in cosmetics and in preservaties.

Toxicology: Harmful if swallowed, inhaled or absoreed through teh skin.  May cause reproductive defects.  Severe eye and skin irritant.

http://www.vaccinetruth.org/2-phenoxyethanol.htm

Harmful by inhalation, in contact with skin and if swallowed. Skin, eye and respiratory irritant. May cause serious eye damage.
Toxicity data
ORL-RAT LD50 1260 mg kg-1 Oral Rat 50% Lethal Dose
SKN-RBT LD50 5000 mg kg-1 Skin Rabbit 50% Lethal
Dose
Irritation data
SKN-RBT 500 mg/24h mld Skin Rabbit 500 mg 24 hours mild
EYE-RBT 6 mg mod Eye Rabbit 6 mg moderate
EYE-RBT 0.25 mg/24h sev Eye Rabbit 24 hours severe
risk phrases
R20 R21 R22 R36 R37 R38 R41.
R20 Harmful by inhalation
R21 Harmful by contact with skin
R22 Harmful if swallowed
R36 Irritating to eyes
R37 irritating to respiratory system
R38 irritating to skin
R41 Risk of serious damage to eyes
Reference:

http://physchem.ox.ac.uk/MSDS/ET/ethylene_glycol_monop
henyl_ether.html
 

2-Phenoxyethanol
Compiled by Cindy Stolten
Parent Advocate and Researcher


Table of Contents:
1. Summary
2. Vaccines containing 2-Phenoxyethanol
3. Toxicology Report on 2-Phenoxyethanol
4. German Study on 18 month old with eczema caused by 2-PE (including references)
5. Web links on 2-PE
a. Government Transcript of the 8/12/99 Workshop on Thimerisol Vaccines
b. PubMed Abstracts
c. Environmental Fact Sheets
d. Efficacy of 2-PE as a preservative

1. Summary:
2-Phenoxyethanol (2-PE) is a chemical substance presently used as a preservative in several vaccines. 2-PE contains phenol, which has the ability to inhibit phagocyte activity, meaning it is toxic to all cells. The phenol in 2-PE is capable of disabling the immune system's primary response mechanism. It can also cause systemic poisoning, headache, shock, weakness, convulsions, kidney damage, cardiac failure, kidney failure, or death. 2-PE also contains ethylene oxide, which is an irritant causing dermatitis, burns, blisters, and eczema.

2. Vaccines containing 2-Phenoxyethanol
Hepatitis A Vaccine, Inactivated
Havrix® SmithKline Beecham Biologicals
http://us.gsk.com/products/assets/us_havrix.pdf
PEDIARIX™
GlaxoSmithKline
http://www.fda.gov/cber/label/dtapsmi121302LB.pdf
DAPTACEL Manufactured by: Aventis Pasteur
http://www.vaccineshoppe.com/US_PDF/DAPTACEL_3973_6.02.pdf
Poliovirus Vaccine Inactivated
IPOL¨ Manufactured by: Aventis Pasteur
http://www.us.aventispasteur.com/PRODUCT/PDFFILES/IPOL.pdf
INFANRIX ® HepB Combined Diphtheria-Tetanus-acellular Pertussis (DTPa) and Hepatitis B Vaccine SmithKline Beecham Biologicals
http://www.gsk.com.au/PDFs/INFANRIXHB.pdf
TETRAVAC® Suspension for i.m. (intramuscular?) Injection - Used only in Germany.
There may be more, but at this time the situation is clouded because of the removal of Thimerasol. There is no way of knowing which vaccines have been replaced with 2-Phenoxyethanol. When the information becomes available it will be added to the site.

3. Toxicology report on 2-Phenoxyethanol
General
Synonyms: phenoxetol, phenoxyethyl alcohol, phenoxyethanol, 1-hydroxy-2-phenoxyethane, rose ether, phenylmonoglycol ether, 2-phenoxyethanol, glycol monophenyl ether, beta-hydroxyethyl phenyl ether, various trade names Uses: Used as a fixative for perfumes, a bactericide (in conjunction with quaternary ammonium compounds), a insect repellent, a topical antiseptic, a solvent for cellulose acetate, dyes, inks and resins, in organic synthesis of plasticizers, in germicides, in pharmaceuticals, in cosmetics and in preservatives.
Molecular formula: C8H10O2
CAS No: 122-99-6
EINECS No: 204-589-7
Physical data
Appearance: colourless or light yellow viscous liquid
Melting point: 14 C
Boiling point: 245 C
Vapour density: 4.76 (air = 1)
Vapour pressure: <0.01 mm Hg at 20 C
Density (g cm-3): 1.102
Flash point: 130 C
Explosion limits:
Autoignition temperature:
Water solubility:
Stability
Stable. Incompatible with acid chlorides, acid anhydrides, strong oxidizing agents. Combustible.
Toxicology
Harmful by inhalation, in contact with skin and if swallowed. Skin, eye and respiratory irritant. May cause serious eye damage.
Toxicity data
ORL-RAT LD50 1260 mg kg-1 Oral Rat 50% Lethal Dose
SKN-RBT LD50 5000 mg kg-1 Skin Rabbit 50% Lethal Dose
Irritation data

SKN-RBT 500 mg/24h mld Skin Rabbit 500 mg 24 hours mild
EYE-RBT 6 mg mod Eye Rabbit 6 mg moderate
EYE-RBT 0.25 mg/24h sev Eye Rabbit 24 hours severe
Risk Phrases
R20 R21 R22 R36 R37 R38 R41.
R20 Harmful by inhalation
R21 Harmful by contact with skin
R22 Harmful if swallowed
R36 Irritating to eyes
R37 irritating to respiratory system
R38 irritating to skin
R41 Risk of serious damage to eyes

Reference:
http://physchem.ox.ac.uk/MSDS/ET/ethylene_glycol_monophenyl_ether.html
4. German Study on 18 month old with eczema caused by 2-PE (including references) Generalized eczema in an 18-month-old boy due to phenoxyethanol in DPT vaccine Thomas Vogt, Michael Landthaler and Wilhelm Stolz
Department of Dermatology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.
Key words: contact hypersensitivity; phenoxyethanol; generalized eczema; drug reactions; DPT vaccine; children; allergen replacement © Munksgaard, 1998.

Lovell et al. (1) reported a case of contact eczema due to 2-phenoxyethanol (2-PE) in aqueous cream. The only other reported cases of 2-PE allergy were seen in Italy (2 cases) (2), The Netherlands (3), and Germany (4). 2-PE has been compared to other preservatives in the guinea pig maximization test (5). All the aforementioned argues for a low risk of sensitization.
An 18-month-old boy was referred with a history of 2 episodes of generalized eczema starting within 24 h of routine administration of DPT (diphtheria, petussis and tetanus) vaccine (Infanrix®, SmithKline-Beecham.)

He had a strong family history of atopic eczema and immediate-type allergy. The dermatitis was more severe the 2nd time, involving the whole body. Treatment with topical corticosteroids cleared it within 1-12 days. However, a 3rd booster vaccination was still required. In addition to the DPT toxoids, Infanrix® vaccine contains polysorbate 80, formaldehyde, aluminium chlorate hexahydrate, aluminium hydroxide, and 2-PE. Patch testing was performed with the complete vaccine and all its individual components in standardized concentrations and vehicles, after the skin of the patient had completely cleared. The irritancy threshold of 2-PE has been determined previously to be>10% (5). The patch test to 2-PE (2% pet.) was positive, showing a crescendo reaction on D2 and D3. A DPT vaccine containing thimerosal as a preservative was therefore used for the subsequent booster (Merioux), to which no skin reaction occurred.

2-PE is effective against a broad spectrum of microorganisms, particularly Pseudomonas aeuginosa (6). As early as 1944, 2-PE-soaked compresses were recommended for skin infections (7), and more recently for gram-negative cellutitis in neutropenic patients (8), and prophylaxis in burns (9). Since 1970, 2-PE has increasingly been added to cosmetics and pharmaceuticals, including vaccines (10). The antimicrobial activity of 2-PE in vaccines is well-documented (11), though it is still not widely used as such in Germany, thimerosal being more commonly used.
2-PE is frequently combined with 1,2-dibromo-2,4-dicyanobutane (DBDCB), in a ratio of 1 (DCDCP): 4 (2-PE), as Euxyl K 400 (12-14). The sensitizing potential of Euxyl K 400 is low compared to Euxyl K 100 (Kathon CG).

References

1. Lovell CR, White IR, Boyle J. Contact dermatitis from phenoxyethanol in aqueous cream BP. Contact Dermatitis 1984: 11: 187.
2. Tosti A, Vincenzi C, Trevisi P, Guerra L. Euxyl K 400: incidence of sensitization, patch test concentration and vehicle. Contact Dermatitis 1995: 33: 193-195.
3. De Groot A C, Bos JD, Jagtman BA. Contact allergy to preservatives (II). Contact Dermatitis 1986: 15: 218-222.
4. Fuchs T, Estenders F, Przybilla B. Contact allergy to Euxyl K 400. Dermatosen .1991: 39: 151-153
5.Hausen B.M. The sensitizing potency of Euxly K 400 and its components 1,2-dibromo-2,4-dicyanobutane and 2-phenoxyethanol. Contact Dermatitis 1993: 28: 149-153.
6. Fitzgerald KA, Davis A, Russell AD. Mechanism of action of chlorhexidine diacetate and phenoxyethanol singly and in combination against gram-negative bacteria. Microbios 1992: 70: 215-230.
7. Gough J, Berry H, Stil BM. Phenoxyethanol in the treatment of pyocyanea infections. Lancet 1944: 2: 176-178.
8. Mitchell P, Powles R, Rege K, Treleaven J. Catovsky D, Mehta J, Jameson B. Phenoxyethanol is effective topical therapy of gram-negative cellutitis in neutropenic patients. J Hosp Infect 1993: 25: 53-56.
9. Lawrence JC, Cason JS, Kidson A. Evaluation of phenoxyethanol-chlorhexidine cream as a prophylactic antibacterial agent in burns. Lancet 1982: 1: 1037-1040.
10. DeGroot AC, Van Ginkel CJ, Weijland JW. Methyldibromoglutaronitrile (Euxl K 400): an important "new" allergen in cosmetics. J Am Acad Dermatol 1996: 35: 743-747.
11. Lowe I, Southern J. The antimicrobial activity of phenoxyethanol in vaccines. Lett Appl Microbiol 1994: 18: 115-116.
12.Bruze M, Gruvberger B, Agrup G. Sensitization studies in the guinea pig with the active ingredients of Euxyl K 400. Contact Dermatitis 1988: 18: 37-39.
13. DeGroot AC, DeCock PA, Coenradds PJ, Van Ginkel CJ, Jagtman BA, Van Joost T, Vander Kley AM, Meinardi MM, Smeenk C, VanderValk PG, Vander Walle HB, Weyland JW. Methyldibromoglutaronitrile is an important contact allergen in The Netherlands. Contact Dermatitis 1996: 34: 118-120.
14 Van Ginkel CJ W, Rundervoort GJ. Increasing incidence of contact allergy to the new preservative 1,2-dibromo-2-dicyanobutane (methyldibromoglutaronitrile). Br J Dermatol 1995: 132: 918-920.

5. Web links on 2-PE
a. Government Transcript of the 8/12/99 Workshop on Thimerosol Vaccines
{PRIVATE }
THE U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
CENTERS FOR DISEASE CONTROL AND PREVENTION
convenes
THE NATIONAL VACCINE ADVISORY COMMITTEE
SPONSORED WORKSHOP ON THIMEROSAL VACCINES
DAY TWO - VOLUME I
AUGUST 12th, 1999
The verbatim transcript of the Sponsored Workshop on Thimerosal Vaccines held Wednesday, August
12th, 1999, at the National Institutes of Health, Lister Hill Auditorium, Bethesda, Maryland.
To read the full transcript of this document go to:
http://216.239.37.100/search?q=cache:cAsu6ZCm1tIC:www.immunizationinfo.org/PDFs/day2_volume1.pdf+Testing+children+for+2-phenoxyethanol+poisoning&hl=en
http://www.immunizationinfo.org/PDFs/day2_volume1.pdf
Quote from Dr. Mary Teeling, Medical Director of the Ireland Medicines Board, during the above workshop: "Perhaps I'm getting old and a bit cynical, but I'm really not sure that we have the full safety picture on 2-phenoxyethanol. It certainly does look to be a safe and efficacious vaccine -- preservative, but we're actually not 100 percent sure about either of these at this point in time. Formaldehyde has also been used. Now, there are other preservatives that have been used in other medicinal products, like benzochromium chloride. I think the important thing is that for a preservative to be used, they must fulfill the European Pharmacopeia specifications. That's a requirement in order to get a license either nationally or at community level in the European Union. So they do have -- So they will, more or less, fulfill the PH Euro requirements. But we're not really -- Ever how much information we have on thimerosal, I think we have less on the others. So you're into a situation, or are you -- You know the phrase, "The devil you know is better than the devil you don't know." And I think that's a very important aspect of this whole review."
b. PubMed Abstracts
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11853695&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11551266&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10959804&dopt=Abstract
Full Study available at:
http://www.whale.to/a/2pe1.html
http://www.whale.to/a/2pe2.html

c. Environmental Fact Sheets
http://www.lakes-environmental.com/toxic/PHENOL.HTML
http://www.epa.gov/opptintr/chemtest/phenoxet.htm

d. Efficacy of 2-PE as a preservative
http://jhs.pharm.or.jp/48(1)/48_89.pdf