Geraniol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Sensitization to skin by geraniol was evaluated in a local lymph node assay (LLNA) performed almost similar to OECD guideline 429 (Lalko, 2006). In this study, groups of four female CBA mice were dosed topically on the dorsum of both ears with 25 µl of geraniol at concentrations of 2.5%, 5%, 10%, 25% and 50% in 1:3 Ethanol:Diethylphtalate. The dosing occurred daily for three consecutive days and two days later all mice were injected intravenously by the tail vein with 250 µl of phosphate buffered saline containing 20 µCi of [3 H] methyl thymidine. A suspensions of the lymph node cells (LNC) was prepared and a stimulation index (SI) for each concentration relative to the concurrent vehicle-treated control was calculated

The EC3 value, or estimated concentration of test material required to elicit an SI of 3 or more, was derived from the dose-response data by linear interpolation. As a result, a dose-dependent induction of LNC proliferation and SI values greater than three at tested concentration of 25% (SI = 4.8) and 50% (SI = 6.0) were noted. Thus, geraniol could be regarded as sensitizing to skin.

In two other LLNA studies by the same author, geraniol was also found sensitizing to skin since the SI values >3 when concentration of 25%, 30% and 50 % were used (Lalko, 2004). In addition, testing with different vehicles (Diethyl phtalate (DEP); 1:3 Ethanol:DEP; 3:1 Ethanol:DEP; Ethanol) revealed that the strength of the sensitization response varied with the vehicle, so that in ethanol even a concentration of 10% also showed a significant positive effect.  

In four studies led by the same author LLNA were conducted according to OECD guideline 429 and guideline EPA OPPTS 870.2600 (Johnson, 2001). In these studies, concentration of 1%, 3%, 10%, 30% and 50% were tested in four CBA/CA/Ola/Hsd mice per dose group. Thereby, the four studies used different vehicles, namely ethanol, diethyl phthalate (DEP), 25% ethanol/75% diethyl phthalate (DEP) and 75% ethanol/25% diethyl phthalate (DEP), respectively. In all vehicles, geraniol was found to result in a SI >3 when concentrations of 30% and 50% geraniol were used. Thus geraniol was regarded as sensitizing.

Although in two other LLNA studies geraniol was found to have no sensitizing effects (Lalko, 2006; Johnson, 2003), further eight were available which found geraniol sensitizing due to induction of LNC proliferation and SI values greater than three (Kimber, 1989, 1991; Basketter, 1997, 1999; Haneke, 2001; Isalo, 2001; Johnson, 2003).

Beside the LLNA studies, several other studies were available, which analyze the sensitization potential of geraniol using the guinea pig maximization test (GPMT), the open epicutanous test (OET), the Freund’s complete adjuvant test (FCAT) or the Draize-test (Basketter, 1997, 1999; Haneke, 2001; Klecak, 1977,1985; Sharp, 1978; Ishihara, 1986; Givaudan, 1977; Quest International, 1989; Buehler, 1992). As a sum of these studies, geraniol could be regarded as sensitizing to skin while the strength of sensitizing effects was concentration-dependent and varied with vehicle used.

This influence of the vehicle was also seen in a study with human where in a modified Draize-test 10% geraniol in ethanol was sensitizing but caused no reaction when applied with petrolatum (Marzulli, 1980). In this study, volunteers received the application of 10 patches which remained in place for 48-72 hours each. After a rest period of 2 weeks, the challenge was done consisting of the application of a 72 hour patch on a new skin site with a nonirritating concentration of geraniol. Whereas in two of 73 subjects a sensitizing effect was noted when applied in ethanol, none of 104 subjects were sensitized by geraniol in petrolatum.

Although in other human studies no sensitizing effect could be detected, these findings were probably results the low concentration of Geraniol used (Schauder, 1997; Ishihara, 1986; Abifadel, 1992). In contrast, several studies performed with subjects previously showing allergic reactions gave positive results in some of these patients, suggesting an sensitizing potential of geraniol in human (Broeckx ,1987; Rudzki, 1986; Emmons, 1985).

In summary, geraniol could be regarded as sensitizing to skin as revealed by several animal studies performed according to guidelines. In addition, several studies with human volunteer, with or without history of allergic reactions, showed sensitizing effects of geraniol. It is also worth to mention, that the sensitizing potential turned out to be concentration-dependent and varied with vehicle.

Migrated from Short description of key information:
- Sensitisation:
Sensitisation: sensitizing in mouse LLNA (OECD 429)

Justification for classification or non-classification

Due to positive results in several LLNA tests and also positive reactions in human studies, Geraniol should be classified as sensitizing. However, human data could not be used to support sub-categorisation either. The present data on dermal sensitization fulfill the criteria laid down in regulation (EU) 1272/2008, and therefore, a classification as Skin Sens 1 (H317) is warranted.