Substance profile

Physicochemical properties

Phenoxyethanol is an oily colourless organic aromatic ether, that is freely soluble in alcohol, ether, and sodium hydroxide. It exists as a liquid at room temperature, and has a vapour pressure of 0.01 mm Hg (20 °C), and is lipophilic (log kOW 1.16).

Kinetics

Following dermal application phenoxyethanol penetrates the skin well and estimates of 80% dermal penetration are suggested for risk assessment (ANSM 2009, 2012).

Following oral administration the pharmacokinetics of phenoxyethanol has been well characterised. Studies in rats indicated that phenoxyethanol is rapidly and near completely absorbed after oral administration and > 90% of the administered dose is excreted in urine within 24 hr post-dosing (BASF, 2007). Phenoxyacetic acid (PhAA) is a major metabolite following oral and dermal routes of exposure to phenoxyethanol in rodents and humans, including preterm infants (BASF, 2007; Bührer, 2002; Howes, 1991). With a plasma half-life of 20–30 min, phenoxyethanol is rapidly and extensively metabolised in the organism by means of alcohol dehydrogenase and aldehyde dehydrogenase via acetaldehyde to PhAA (Johnson and Johnsson, 1990; Gross et al, 2009).

Toxicity

This report focuses on exposure, therefore, a detailed review of the toxicological data on phenoxyethanol and choice of critical study for the risk assessment is beyond the scope of this report. However, a brief review of the key toxicity data is provided in order to provide an example of the risk assessment using the different exposure scenarios.

Phenoxyethanol has low acute toxicity. Numerous repeated dose toxicity studies in laboratory animals have been conducted on phenoxyethanol (briefly described in Troutman et al, (2015)). Based on these studies the target organs for toxicity are the hematopoietic system, liver and kidneys. From the entire data set of subchronic and chronic studies for phenoxyethanol, the lowest reported LOAEL is 400 mg/kg/day based on renal changes observed in a subchronic rat oral gavage study. The highest oral NOAEL below this oral LOAEL in the same species is the NOAEL of 369 mg/kg/day from a subchronic rat drinking water study, which is a suitable point of departure for the hazard assessment.

Phenoxyethanol was negative for genotoxicity in several in vitro (bacterial reverse mutation, mammalian cell cytogenetics, and gene mutation assays) and in vivo (chromosomal aberration (cytogenicity) and mouse micronucleus assay) studies. Two drinking water carcinogenicity studies in rats and mice demonstrated no increased incidence of tumours resulting from chronic exposures to PhE in rats and mice. A dermal developmental toxicity study in rabbits resulted in no teratogenic or developmental effects when administered at doses of up to 600 mg/kg bw/day. In addition, a two generation oral feeding study in mice revealed a parental NOAEL of 1875 mg/kg bw/day and an offspring NOAEL of 375 mg/kg/day.