Reaction mass of 2,6-Octadien-1-ol, 3,7-dimethyl-, (E) and 2,6-Octadien-1-ol, 3,7-dimethyl-, (Z)-

Endpoint summary

Description of key information

- Irritation
Skin: irritant for rabbit skin (OECD 404)
Eye: irreversible effects for rabbit eye (OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Additional information

Skin

Geraniol

The irritation to skin by geraniol was analyzed in a study with three experiments performed according to OECD guideline 404 as stated in the ECETOC Technical Report No. 66 (Givaudan, 1995). In these experiments, 0.5 ml of geraniol was applied to three to four rabbits for 4 h and the application site was observed the following 7 days. Resulting erythema and edema were scored 24, 48 and 72 h later, as well as 7 days after application and scored according to Draize. The results were erythema scores of 2, 2.08 and 1.92 and edema scores of 1.67, 1.25 and 1 in the experiments 1, 2 and 3, respectively. Since the irritation effects were still apparent and desquamation was noted at the end of observation time, geraniol could be regarded as irritant to skin.

In another study performed according OECD guideline 404, intact skin of three New Zealand white rabbits as applied with two types of geraniol (Geraniol 5020 and Geraniol 980) under semiocclusive conditions for 4 h (BBA, 1987). As a result, the primary dermal irritation index (PDII) was found to be 3.8 for Geraniol 5020 and 2.2 for Geraniol 980.

A Draize-test was conducted with 12 angora rabbits, where 0.1 g of geraniol besides two other substances was applied to clipped skin under occlusive conditions for 24 h (Motoyoshi, 1979). The resulting effects was and PDII of 3 after 48 h. In the same study, six Hartley guinea pigs and six Pitman-Moore improved strain miniature swines were also tested and PDII of 3 was found in guinea pigs whereas in miniature swine no irritation was noted (Motoyoshi, 1979).

In addition to the described studies, several other publications and studies by companies showed that geraniol is irritant to skin (Sharp, 1978; Haynes, 1984, 1985, 1986; Klecak, 1977; Troy, 1977; Givaudan, 1977; Buehler, 1992; Givaudan, 1977; Quest International, 1980, 1989). Because of this pronounced irritant effects, geraniol was also used as a positive control in numerous skin irritation studies with other substances performed by Quest International.

Besides this, skin irritation was also tested in a direct topical application test and patch test on the SkinEthic Model reconstituted human epidermis (Tornier, 2006). Since in both test types low cell viability, necrosed histology and an increase of the amount of IL-1alpha was detected, geraniol was regarded as irritant to skin.

When geraniol was tested with human volunteers, a concentration of 32% applied for 48 h induced severe skin irritation when evaluated 30 min after patch removal (Motoyoshi, 1979).

In another study, 0.2 ml was a applied progressively from 15 and 30 minutes through 1, 2, 3 and 4 hours to the upper arm of 25 volunteers (York, 1996). In two subjects severe irritation effects were observed after the 4 h exposure period.

Concentrations of 0.5%, 2% and 20% did no cause any irritation to the skin of 84, 30 and 29 subjects, respectively (Fujii, 1972).

In summary, geraniol could be regarded as irritant to skin as demonstrated in numerous animal studies. The grade of severity could be thereby linked to the concentration used as observed in the studies with human. 

Nerol

Skin irritation was evaluated in a study which performed under GLP according to OECD guideline 404 (Bush Boake Allen Inc., 1987). Thereby, 0.5 ml of pure nerol was applied to the clipped dorsal flank area of three New Zealand White rabbits for four hours under occlusion. Since erythema was observed during the seven day observation period and hyperkeratinization of all the treated skin sites was noted on day 7, nerol was found to be irritant to rabbit skin.

The same result was found in another study, where 5000 mg/kg bw were applied to clipped, abraded abdominal skin of ten New Zealand White rabbits for 24 h under occlusive conditions (Moreno, 1972). Because moderate erythema and edema were observed in almost all animals from 24 to72 h and at the end of the seven day study period, nerol was found to be irritant to skin.

In an irritation screen prior to a Buehler delayed contact hypersensitivity test, nerol at concentrations of 0.5%, 1%, 2.5%, 5%, 10%, 25%, 50% and 100%. in diethylphtalate were tested (Buehler, 1992). 0.3 ml each was applied to the clipped back of four female and four male Hartley guinea pigs for 6 h under occlusion. As result, slight but confluent or moderate patchy erythema to moderate erythema were noted.

In a Draize-test, 0.5 ml of nerol was applied to the shaved dorsal area of nine rabbits for 24 h (Troy, 1977). As a result, a mean irritating score of 0.67 was reported indicating that nerol was not irritating under the condition of that study.

In addition to studies with animals, a pre-test for human maximization studywas available, where nerol at 4% in petrolatum was applied via a closed-patch onto the backs of 5 male volunteers for 48 h (Kligman, 1972). As a result, no irritant effects were observed.

Eye

Geraniol 

Irritation to eyes by geraniol was evaluated in a study performed according to OECD guideline 405 and EU method B.5 (Haarmann und Reimer, 2000). 0.1 ml of pure geraniol was administered into the right eye of four SPF albino rabbits and reactions were monitored for 21 days. Well defined signs of irritation were observed on the treated eyes, including cornea opacity, iris lesion, crimson red conjunctiva and swelling of the conjuctiva, while they were not reversible in two out of four animals after the observation period. Thus, geraniol could be regarded as irritant to eyes.

In another study, a Draize-test was performed where 0.1 ml of geraniol was applied into the eyes of six rabbits (Troy, 1977). Irritant effects were noted during the observation period of seven days, so geraniol was regarded as irritant to eyes.

When geraniol at a concentration of 12.5%was instilled into the eye of three albino rabbits, no corneal opacity or iris congestion was observed, but an intense conjunctival irritation was observed involving chemosis and discharge (IFF, 1963). In the same study, only a mild conjunctival irritation was noted, when a concentration of 5% was used.

Thus, geraniol could be regarded as eye damaging due to results in studies including a study performed according OECD guideline.

Nerol

When 0.1 ml of nerol was instilled into the eyes of six rabbits (Troy, 1977), nerol was found to be irritant to eyes.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irreversible effects

Justification for classification or non-classification

Due to results of studies for skin irritation and for eye irritation, Geraniol 60 has to be classified according to Regulation (EC) No 1272/2008 as irritant to skin Cat. 2 (H315) and as eye damaging Cat 1 (H318).