Phenoxyethanol

WHAT IS PHENOXYETHANOL?

Phenoxyethanol is commonly used as a preservative in various products such as medicines (e.g. in vaccines) or in biocidal products such as hand disinfectants up to a concentration of 5%, including use in products for toddlers.(1) In Europe, it is authorised in cosmetic formulations at a maximum concentration of 1.0%.(2) In France, the French National Agency for the Safety of Medicines and Health Products (ANSM) advise not to use phenoxyethanol on the nappy area (including wipes), for children under 3 years old.(3)

Phenoxyethanol has a large spectrum of antimicrobial activity and is effective against various Gram-negative (including Pseudomonas aeruginosa) and Gram-positive bacteria, as well as against yeasts. Phenoxyethanol has only a weak inhibitory effect on resident flora.(2)

WHY ARE THERE SAFETY CONCERNS AROUND ITS USE IN COSMETIC PRODUCTS?

Doubts on the safety of phenoxyethanol have arisen due to concerns and assimilation to the whole glycol ether family, some of which have different chemical and physical properties.(4) Some of these are classified as reproductive toxic substances and are banned from cosmetics in Europe under Regulation (EC) No. 1272/2008.

Furthermore, controversial claims over whether phenoxyethanol has negative effects on the blood and liver, as well as endocrine disruption have also been a matter of public debate, particularly in the media and lay public.

PHENOXYETHANOL IS RAPIDLY ABSORBED AND METABOLISED

Studies show that phenoxyethanol is rapidly absorbed, distributed, metabolised and excreted.(2, 5-8) It is almost completely absorbed through the skin and is metabolised either by the skin or the liver into its metabolite 2-phenoxyacetic acid.

After a 24-h exposure, very small amounts (<0.1%) remain in the different layers of the skin and most phenoxyethanol is recovered in receptor fluid, indicating that phenoxyethanol does not bind or accumulate in the skin.(2)

PHENOXYETHANOL DOES NOT CAUSE SYSTEMIC TOXICITIES AT DOSES USED IN COSMETICS

The toxicity of phenoxyethanol has been extensively studied in repeated dose animal studies, via inhalation, oral and dermal routes of administration.

Oral exposure to high doses of phenoxyethanol has been associated with systemic effects including anaemia, and decrease in cholesterol and phospholipid levels.(2) Systemic effects such as hematologic and liver effects have been observed after oral exposure of high doses of phenoxyethanol. Both the oral route and the high doses used in these animal studies make these data irrelevant compared to the routes and dosages of phenoxyethanol as used in cosmetic products.(2)

Three studies assessed the toxicity of phenoxyethanol in rabbits through dermal administration at high doses: 2 of them showed no systemic effects up to a maximum tested dose of 1000 mg/kg bw/day; one has been associated with haematological effects at 600 mg/kg bw/day.(2, 9) However this dose of phenoxyethanol is the equivalent of 200-fold the applied daily dose of cosmetics used in humans. Furthermore, rabbit skin is more permeable to phenoxyethanol, there is a higher sensitivity of rabbit red blood cells to phenoxyethanol, and a lower capacity to metabolise phenoxyethanol compared to other species, including humans. Consequently, haematological effects due to topical exposure to phenoxyethanol as reported in rabbit studies are not relevant for humans.(2)

PHENOXYETHANOL DOES NOT AFFECT THE REPRODUCTIVE SYSTEM

Phenoxyethanol is not classified as a reproductive toxic substance. In animal studies, no effects on reproductive and developmental parameters were observed.(2)

PHENOXYETHANOL DOES NOT HAVE CARCINOGENIC POTENTIAL

The carcinogenic potential of phenoxyethanol was assessed in two carcinogenicity studies conducted via the oral route in rodents.(2)No carcinogenic effects were observed in either of these studies.

THERE IS NO SCIENTIFIC EVIDENCE OF THE ENDOCRINE DISRUPTION POTENTIAL OF PHENOXYETHANOL

Three publications (all part of the same cohort observational study), have investigated the endocrine disruption potential of phenoxyethanol. These three reports did not confirm that phenoxyethanol had endocrine disruption potential.

The first study did not show any association between phenoxyacetic acid (primary metabolite of phenoxyethanol) and cryptorchidism or hypospadias.(4)The two remaining studies did not provide sufficient evidence for plausible association between phenoxyacetic acid and changes in sex hormone-binding globulin (SHBG), androgenic and estrogenic activities in newborns.(10, 11)

The studies also did not report any effect on thyroid hormone pathways. Furthermore, the ANSM concluded that these data cannot be used to support the endocrine disruption potential of phenoxyethanol.(3)

PHENOXYETHANOL IS NOT ASSOCIATED WITH NEUROLOGICAL EFFECTS

Animal studies have demonstrated that phenoxyethanol is not associated with neurotoxic effects, irrespective of the route of administration. Human studies are scarce and no conclusion can be drawn due to numerous limitations.(12, 13)

PHENOXYETHANOL IN COSMETIC USE HAS NO LOCAL SIDE EFFECTS

Phenoxyethanol has been shown to produce signs of eye irritation, when administered undiluted in 3 rabbits, with a maximal irritation 72 h after administration. (2) Undiluted phenoxyethanol is never used in the production of cosmetics.(1) Studies in humans have not demonstrated any local or systemic effects after the use of phenoxyethanol on injured skin.(14, 15) Furthermore, 2% phenoxyethanol when used as a disinfectant is well tolerated in premature neonatal skin. Only one study, conducted in premature infants with extreme low birth weights, showed some signs of skin irritation with a topical antiseptic solution containing both 0.1% octenidine and phenoxyethanol (concentration is not reported).(16) The ANSM has evaluated other studies in its assessment and reports that irritation reactions to phenoxyethanol have not been observed in humans.(3)
Although phenoxyethanol is present in a large variety of rinse-off and leave-on cosmetic products, sensitisation reactions (i.e. contact urticaria) in humans are very rare. Phenoxyethanol is not classified as a sensitizer by the ECHA.

CONCLUSION: PHENOXYETHANOL CAN BE CONSIDERED AS ONE OF THE MOST WELL- TOLERATED PRESERVATIVES USED IN COSMETIC PRODUCTS

The SCCS states that phenoxyethanol is safe for all consumers including children at all ages when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in animal studies only at exposures magnitudes higher than usual consumer exposure (i.e. 200-fold higher than doses used in humans).