Human metabolism and excretion kinetics of the fragrance 7-hydroxycitronellal after a single oral or dermal dosage.

Abstract

7-Hydroxy-3,7-dimethyl-1-octanal, also known as 7-hydroxycitronellal (7-HC, CAS No. 107-75-5) is a synthetic fragrance widely used in cosmetic and hygiene products. Due to its large scope, 7-HC was selected for the development of a biomonitoring method suitable for the general population within the frame of the cooperation project between the German Federal Ministry for the Environment (BMUB) and the German Chemical Industry Association (VCI). In a human study with 5 healthy subjects who received single dermal and oral doses 7-HC, suitable metabolites and their urinary excretion kinetics was investigated. Two metabolites of 7-hydroxycitronellal were identified in urinary fractions after dermal and oral dosing: The alcohol 7-hydroxycitronellol (7-HCO) and the corresponding acid 7-hydroxycitronellylic acid (7-HCA). Only 7-HCA proved to be a suitable biomarker of exposure to 7-HC, since 7-HCO was quantifiable in only a minority of urine samples collected from the general population. Quantification of 7-HCA was conducted by means of a newly developed UPLC-MS/MS (ultra-high pressure liquid chromatography combined with tandem mass spectrometry) method. Peak excretion of 7-HCA occurred between 3 and 5h after oral application and about 10h after dermal administration. Due to the limited skin absorption of 7-HC, 7-HCA concentrations after dermal application were much lower than levels after oral application. After 24h, about 9% and 50% of the dermally and orally applied dose, respectively, were excreted as 7- HCA. With the conversion factors derived from the controlled human study, we estimated median exposure doses in a group of 40 human volunteers from the general population of approximately 93μg 7-HC per day. In conclusion, the 7-HC metabolite 7-HCA in urine is a suitable biomarker of exposure and can be applied for biomonitoring of the general population.