Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

Skin irritation:

As key study for skin irritation a publication of the ECETOC Task Force was chosen (Bagley, 1996). They developed a data bank for irritant and corrosive chemicals containing 176 chemicals. Pursuant to this publication, dl-Citronellol was tested according to OECD Guideline 404 and under GLP conditions in a single-patch test (three rabbits) as well as in two multi-patch tests (four rabbits for each experiment) by applying 0.5 ml of 98.7% dl-Citronellol to the skin under semiocclusive condition for 4 h. Readings of erythema and edema scores were done at 24, 48, 72 h and 7 days after start of exposure. Indications of skin irritation were found with mean erythema score of 2.0 (single- and multi-patch test) and edema score of 2.2 (single-patch test) and 2.0 (multi-patch test) calculated over all the animals tested. After 7 days, reversibility of irritation was not observed in any of the animals tested. Seven animals showed a slight improvement in erythema and edema scores, however three animals showed no improvement and one animal shows a worsening of the symptoms. Desquamation was apparent in 8 out of 11 animals.

In a comparative study with rabbits, guinea pigs and miniature swine, 0.1 g citronellol was applied to skin of twelve angora rabbits under occlusive condition for 24 h (Motoyoshi, 1979a). 30 min after evaluation of the application sites, a second application followed. As result severe irritant effects were noted and a primary irritation index (PII) of 3 was calculated. When the same protocol was used for a test with six guinea pigs, also a PII of 3 was found, reflecting the observed irritating effects (Motoyoshi, 1979b). In contrast, application of 0.05 g Citronellol to the clipped dorsal skin of six miniature swine under occlusion for 48 h did not result in irritant effects (Motoyoshi, 1979c).

Further in vivo studies from secondary source with limited documentation (reliability 4) confirm the irritant properties of Citronellol observed in the key study described above.

 

In addition to studies with animals, studies with human are also available for assessment.

In one study, a 24 hour closed patch test with undiluted test material was conducted with male and female volunteers and no irritant reactions were found (Katz, 1946).

In another study, citronellol was applied at a concentration of 32% in acetone to the back of volunteers (Motoyoshi, 1979). After 48 h the patch was removed and sites were evaluated, which was repeated at 72, 96, and 120 hours after patch removal if necessary. As result, citronellol at 32% was found to be moderately irritating, meaning 40%-70% of sites showed positive reactions.

When 0.2 ml citronellol was applied to the skin of the upper outer arm of 30 human volunteers for 4 h, no irritant effects were found (Basketter, 2004).

Further human studies from secondary source with limited documentation (reliability 4) reported irritant effects of Citronellol depending on test substance concentration.

 

In addition, in vitro studies with Citronellol were performed. A skin integrity function test (SIFT) showed no irritant effects (Heylings, 2003), whereas in studies with human skin models i.e. EpiDerm, Episkin and SkinEthic citronellol was found to be a skin irritant (Fentem, 2001; Portes 2002; Tornier 2006).

 

Overall in a weight of evidence, Citronellol is considered to be irritating to skin.

 

Eye irritation:

Eye irritation was evaluated performing a Draize-test similar to OECD guideline 405. In this study, six Vienna White rabbits received an application of 0.1 ml Citronellol into the conjunctival sac of the lower right eyelid. Readings were done at 24, 48, 72 h and 8 days after start of exposure (BASF, 1979). As result, scores for cornea, iris, conjunctivae and chemosis were found to be 1.0, 0.28, 1.72 and 1.44, respectively. Iris and chemosis were reversible at the end of the observation period of 8 days in all animals, whereas conjunctival redness and corneal opacity were not fully reversible within this period. However, it can be assumed that these effects would be reversible if the observation period would have been extended up to 21 days.

 

An in vivo study with New Zealand rabbits from secondary source with limited documentation (reliability 4) confirms the eye irritant properties of Citronellol observed in the key study described above.

Justification for classification or non-classification

Skin irritation:

The present data fulfill the criteria laid down in 67/548/EEC and 1272/2008/EEC, and a classification "irritating to skin" (R38) and "skin irritant" (Category 2) is warranted.

Eye irritation: The present data on eye irritation do not fulfill the criteria laid down in 67/548/EEC. According to 1272/2008/EEC, a classification as "irritating to eyes" (Category 2) is warranted.