Geranyl acetate

Endpoint summary

Additional information

No valid in vivo experimental data are available for the assessment of the toxicokinetics, metabolism and distribution of geranyl acetate.

Based on its physicochemical properties, i.e. small molecular weight, Log Pow and low to moderate water solubility at room temperature (MW = 196.29, Log Pow = 4.04; water solubility = 29 mg/L), geranyl acetate is considered to become readily bioavailable via the dermal and oral route. On the basis of the low vapour pressure at room temperature (vapour pressure = 1.3 Pa), the exposure via inhalation of geranyl acetate as a vapour is low. Oral bioavailability of geranyl acetate is qualitatively indicated by mortalities and clinical findings observed in acute oral toxicity studies in rats and systemic effects observed in murine and rat oral repeated dose toxicity studies.

Evidences for a dermal penetration is given in literature from secondary sources. These studies were not performed according to current standard protocols but give some indication for a moderate dermal penetration potential of geranyl acetate. An indirect detection via the assessment of dermal Eserine penetration in mice provided evidence of a dermal penetration potential of geranyl acetate (Meyer 1959). Increased viscosity of aged geranyl acetate was found to decrease dermal uptake according to the given testing setup.

An indirect detection of dermal geranyl acetate penetration via detection of penetrated rhodamine provided evidence of a dermal uptake of geranyl acetate into epithelium and hair follicles, but not in corium and subcutis after application for 2 hours in guinea pigs (Meyer 1965). Based on the given criteria, a genuine penetration defined as active principle detected in corium or subcutis was not observed.

Concerning metabolism of geranyl acetate, the hydrolysis and degradation of Geranylacetat Extra in plasma, liver and gastrointestinal tract was investigated in an in vitro study (BASF SE 09B0294/09B019, 2013). To determine hydrolysis in either compartment, the test substance was incubated at a nominal concentration of 250 µM for 0.5, 1 and 2h at 37°C in plasma, liver S9 fraction, gastric-juice simulant and intestinal-fluid simulant including pancreas lipase. After incubation, the proteins in the so called active incubates (AI) were precipitated by the addition of acetone and the amount of remaining substrate was analysed in the supernatant by GC/FID. Heat deactivated controls (HDC, with the exception of gastric juice simulant) and controls, directly stopped after addition of test substance (t=0 control) served as control samples. It has been demonstrated that Geranylacetat Extra is hydrolyzed within 0.5 h to Geraniol almost completely in rat plasma, liver S9 fraction of rats and intestinal- fluid simulant under the test conditions used. In gastric fluid simulant the degradation of Geranylacetat Extra was slower and was calculated to be about 50% after an incubation period of 2 h. The degradation of Geranylacetat Extra yielded maximum degradation rates of ≥211.8 [µmol/L*h], ≥2.7 [µM/g liver equivalent*h], ≥21.3 [µM/g pancreas lipase (15-35 U/mg)*h] and 93.2 [µmol/L*h] for rat plasma, liver S9 fraction of rats, intestinal fluid simulant containing 1 weight% pancreas lipase and gastric fluid simulant, respectively. These maximum degradation rates of Geranylacetat Extra were in the same order of magnitude than the maximum degradation rates determined for the positive control Benzyl benzoate.

In addition, the following information is taken from the revised test plan for Terpenoid Primary Alcohols and Related Esters (The Flavor and Fragrance High Production Volume Consortia - The Terpene Consortium; March 2004):

Geranyl acetate is expected to hydrolyze to geraniol and acetic acid. In animals hydrolysis of aliphatic esters is catalyzed by classes of enzymes recognized as carboxylesterases or esterase. Structurally similar citronellyl acetate was reported to be completely hydrolyzed within 2 hours by simulated intestinal fluid containing pancreatin at pH 7.5. Terpenoid alcohols formed in the gastrointestinal tract are then rapidly absorbed. Following hydrolysis, geraniol, nerol, and citronellol undergo a complex pattern of alcohol oxidation, omega-oxidation, hydration, selective hydrogenation and subsequent conjugation to form oxygenated polar metabolites, which are rapidly excreted primarily in the urine of animals. Alternately, the corresponding carboxylic acids formed by oxidation of the alcohol function may enter the beta-oxidation pathway and eventually undergo cleavage to yield shorter chain carboxylic acids that are completely metabolized to carbon dioxide. Geraniol, related terpenoid alcohols (citronellol and nerol), and the related aldehydes (geranial and neral) exhibit similar pathways of metabolic detoxication in animals.

Based on the information given above, there is no evidence for a bioaccumulative potential of geranyl acetate.