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Toxicological information

Sensitisation data (human)

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

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The review of Lalko and Api (2008) compiled data from 5 human repeat insult patch tests (HRIPT; unpublished RIFM studies) and 14 human maximization tests (HMT) which are exclusively cited from unpublished RIFM reports.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.

Applicant's summary and conclusion