Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Additional information:

Skin sensitization

In the chosen key study, i.e. a Local Lymph Node Assay according to OECD 429 and GLP, geranyl acetate has been applied to CBA/CaOlaHsd mice undiluted or at 50% and 25% in acetone/olive oil (4+1 v/v) (BASF 2013). Application of geranyl acetate did statistically significant alter ear weights at all concentrations tested, being indicative for dermal irritation potential of the test substance. An clear dose response increase in 3HTdR incorporation has been observed leading to stimulation indices (S.I.) of 4.95, 7.33 and 7.56 for the 25%, 50% and 100% dose group respectively. In line, lymph node weights and lymph node cell counts were increased in these dose groups, when compared to the vehicle control. Overall, geranyl acetate has been found to be a skin sensitizer under the chosen testing conditions.

In contrast, in an open epicutanous test (OET) not according current test guidelines and with limited documentation, guinea pigs received 21 daily epicutaneous applications of 0.1 ml test substance (concentration not specified; Klecak, 1985). At days 21 and 35 after beginning of the induction period, challenge applications with geranyl acetate at a concentration of 4% were performed. According to the authors, geranyl acetate was reported to be negative and therefore no skin sensitizer under the given testing conditions. 

In a closed epicutaneous test (CET), i.e. a publication with limited documentation (predominantly in japanese), guinea pigs were repeatedly treated with occluded epidermal applications of 10 % geranyl acetate for 48 hr (3 times per week for 2 weeks) for induction (Ishihara, 1986). Following a 2 week rest period, challenge was performed in terms of occluded epidermal application of 10% geranyl acetate for 48 hrs. According to the authors geranyl acetate was not skin sensitizing under the chosen testing conditions. Furthermore, the results of a human maximization test (induction/challenge concentration = 4% geranyl acetate) were reported in tabular form, showing no evidence of skin sensitization (rate 0/25).

 

In addition to studies with animals, several human studies with geranyl acetate and the resepective stereoisomer neryl acetate reported as short summaries from secondary source were available for assessment of skin sensitization.

In an repeated insult patch test, 25 volunteers received five application of 4% geranyl acetate for 48 each onto sodium lauryl sulfate pretreated skin sites (Greif, 1967). After a rest period of ten days, a challenge application for 48 was given. As a result, none of the 25 subjects showed sensitization reactions.

In a human maximization test with 25 male volunteers 10% neryl acetate (stereoisomer of geranyl acetate ) in petrolatum was applied with an occlusive patch 5 times for 48 h on the forearms pretreated for 24 hours with 5% aqueous sodium lauryl sulfate (Kligman 1972). Following a 10-day rest period, challenge patches were applied under occlusion to fresh sites for 48 hours. The challenge applications were pretreated for 1 hour with 10% aqueous sodium lauryl sulfate under occlusion. No skin reactivity was observed on any subject during the study. Therefore neryl acetate did not show any evidence of induced allergic contact dermatitis in human subjects under the given study conditions

In a patch test with 20 male and female perfume-sensitive patients, geranyl acetate was tested at 2% in petrolatum using aluminum back strips for 48 h and reactions were read 24 h later (Larsen, 1970). No skin reactions were reported.

In a patch test, 187 male and female Japanese patients were tested with concentrations of 0.05 - 0.5% neryl acetate (stereoisomer of geranyl acetate) on the back, forearm and inside of the upper arm under occlusion (Takaneka, 1986). After the exposure duration of 24 - 48 h, reactions were scored 30 min after removal of the patch. Skin reactions were observed: 3/187 exhibited erythema and 5/187 exhibited slight erythema.

However, in a patch test from the same authors using geranyl acetate, 265 male and female Japanese patients were tested with concentrations of 0.05 - 0.5% geranyl acetate on the back, forearm, or inside of the upper arm under occlusion (Takaneka, 1986). After the exposure duration of 24 - 48 h, reactions were scored 30 min after removal of the patch. As result, none of the 265 subjects showed sensitization effects.

In a patch test reported in a publication with limited documentation, 2 patients with contact dermatitis to Oil of Citronella showed dermal reactions after application of 1% geranyl acetate in acetone, whereas 14 patients with a variety of skin ailments unrelated to Citronella oil did not show any skin reactions after such a treatment (Keil, 1947). In a patch test with 165 dermatoses patients, the application of 0.4% geranyl acetate did not result in any skin reactions (Fujji 1972).

Respiratory sensitisation

Endpoint conclusion
Additional information:

No data available.

Justification for classification or non-classification

The present data on dermal sensitization fulfill the criteria laid down in 67/548/EEC and regulation (EU) 1272/2008, and therefore, a classification with R43 and "Skin sensitisation" (Category 1) is warranted.