Citronellal

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

other: Review article

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Reevaluation of data from sensitisation assays with citral both in humans and test animals, compiled data are both from reliable published studies and from RIFM study reports which are not publically available; review acceptable for identifying a threshold for sensitisation

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

review article or handbook

Title:

Citral: Identifying a threshold for induction of dermal sensitization

Author:

Lalko J, Api AM

Year:

2008

Bibliographic source:

Reg Toxicol Pharmacol 52: 62-73

Materials and methods

Type of sensitisation studied:

skin

Study type:

study with volunteers

Principles of method if other than guideline:

Human repeated insult patch test (general principle): induction by nine 24-h occluded applications within 3 weeks, 2 week rest period, challenge by single 24-h patch
Human maximization test (general principle): induction by 5 alternate day 48-h occluded patches, 10 to 14-day rest period, challenge by 48-h patch

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Citral

EC Number:

226-394-6

EC Name:

Citral

Cas Number:

5392-40-5

Molecular formula:

C10H16O

IUPAC Name:

Reaction mass of (E)-3,7-dimethylocta-2,6-dienal and (Z)-3,7-dimethylocta-2,6-dienal

Constituent 2

Reference substance name:

(Z)-3,7-dimethylocta-2,6-dienal

EC Number:

203-379-2

EC Name:

(Z)-3,7-dimethylocta-2,6-dienal

Method

Type of population:

general

Results and discussion

Results of examinations:

NOEL of 1400 µg/cm2

Any other information on results incl. tables

Sensitisation data in humans

The review of Lalko and Api (2008) compiled data from 5 human repeat insult patch tests (HRIPT; unpublished RIFM studies) and 14 human maximization tests (HMT) which are exclusively cited from unpublished RIFM reports. Furthermore various clinical diagnostic patch tests with citral have been assessed.

Evaluation of human maximization test (HMT)data:

In all but one HMT, citral induced sensitisation at test concentrations ranging from 4 to 8% corresponding to 2759 to 5517 µg/cm²citral in petrolatum. Overall, a decrease in the incidences of positive responses have been observed by increased doses. In a single HMT conducted with 2% (1379 µg/cm2) citral in petrolatum on 24 male volunteers, sensitization reactions (2/24) were observed.

Evaluation of human repeated insult patch test (HRIPT) data:

Test concentrations in the different studies covered a range of 388 to 3876 µg/cm²;

No sensitising effects were observed up to 1400 µg/cm²; A sensitisation rate of 5/8 was observed at the highest test concentration of 3876 µg/cm²

Overview on diagnostic patch tests with citral*:

 *The table is restricted to the literature reports of clinical diagnostic patch tests to citral in greater than 100 consecutive patients.

Concentration/Vehicle	Results	References
5% in petrolatum	4/155 cosmetic dermatitis patients	Ishihara et al. (1981)
	5/159 eczema/dermatitis patients
	0/48 control subjects
5% VNR	8/310 cosmetic dermatitis patients	Itoh et al. (1986, 1988), Nishimura et al.(1984)
	9/408 non-cosmetic patients
	1/122 control subjects
2% VNR	21/1825 patients	Frosch et al. (2002)
2% in petrolatum	19/1825 patients	DeGroot et al. (2000)
2% VNR	12/1701 patients	Frosch et al. (2004, 2005)
2% VNR	28/658 patients	Heydorn et al. (2002, 2003a,b)
2% VNR	1/240 cosmetic dermatitis patients	Itoh et al. (1986, 1988), Nishimura et al.(1984)
	2/584 non-cosmetic patients
	0/105 control subjects
1% VNR	6/1701 patients	Frosch et al. (2004, 2005)
1% VNR	4/228 patients	Mitchell et al. (1982)
1% in petrolatum	8/192 patients	Frosch et al. (1995)
0.1% VNR	1/192 (reaction was questionable) patients	Frosch et al. (1995)

Abbreviations: VNR = vehicle not reported.