Fragrance Compound Geraniol Forms Contact Allergens on Air Exposure. Identification and Quantification of Oxidation Products and Effect on Skin Sensitization

Abstract

Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.

Impact of different storage conditions on the quality of selected essential oils

“…Effect of varying storage conditions on physico-chemical properties and HPLC-fingerprints of selected essential oils Determination of POV has been formerly proposed for quality control of essential oils (Wabner, 2002). To some degree, POVs reflect the amount of oxidizing compounds in the oil at the time of measurement such as hydroperoxides, which themselves have been considered responsible for allergic skin reactions to flavoring materials (Hagvall et al, 2007;Hellerström, Thyresson, Blohm, & Widmark, 1955;Karlberg, Shao, Nilsson, Gäfvert, & Nilsson, 1994;Pirilä & Siltanen, 1958;Sköld et al, 2004). However, decreasing values due to peroxide degradation into more stable oxidized secondary products have been reported (e.g., Bernhard & Marr, 1960;Haddouchi et al, 2011;Pirilä & Siltanen, 1958), feigning a false state of freshness of the sample analyzed.…”

“…This may lead to shifting color, an increase in viscosity or the formation of an unpleasant, often pungent aroma by changes in composition and a rise of oxidized compounds, the so-called "off-flavor". Moreover, terpenoid oxidation products may even cause allergic skin reactions while their non-oxidized counterparts are not or only scarcely irritating (Bråred-Christensson, Forsström, Wennberg, Karlberg, & Matura, 2009Bråred-Christensson, Matura, Gruvberger, Bruze, & Karlberg, 2010;Hagvall et al, 2007;Hausen, Reichling, & Harkenthal, 1999;Matura et al, 2005;Pirilä & Siltanen, 1958). Nevertheless, only few studies have been performed to comprehensively assess the impact of storage conditions on the stability of essential oils (Braun & Franz, 1999;ElNikeety, El-Akel, Abd El-Hady, & Badei, 1998;El-Wakeil et al, 1986;Fincke & Maurer, 1974;Haddouchi, Chaouche, Lazouni, & Benmansour, 2011;Misharina & Polshkov, 2005;Misharina, Polshkov, Ruchkina, & Medvedeva, 2003;Nguyen et al, 2009;Tóth, 1967), while HPLC was hitherto not addressed in this regard except for quantification of selected hydroperoxides (Hagvall, Sköld, Bråred-Christensson, Börje, & Karlberg, 2008).…”

Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK

“…In the present study, treatment with geraniol significantly reduced the serum MDA activity and increased the serum activities of SOD, GSH and GSH-PX in SCI rats. Hagvall et al (29) indicated that geraniol affects skin sensitization through anti-oxidation. Prasad and Muralidhara (30) also revealed that geraniol may be a promising therapeutic candidate that acts by reducing the levels of oxidative markers in the management of diabetic neuropathy in humans.…”

Quantitative risk assessment of the aggregate dermal exposure to the sensitizing fragrance geraniol in personal care products and household cleaning agents

“…Oxidation products of geraniol have been shown to be stronger sensitizers than the mother compound (Hagvall et al, 2007(Hagvall et al, , 2013. In every-day life consumers are likely exposed to (partly) oxidized geraniol, as containers are opened by the consumer and used for a longer time period.…”

“…Of six LLNA experiments listed in Table 8 the underlying data are available (Lalko andApi, 2006, Lalko et al, 2004;Hagvall et al, 2007). Cellular proliferation was determined using incorporation of [ 3 H]thymidine in the lymph nodes, which was measured by counting disintegrations per minute (DPM) per node for each experimental group.…”