Registration Dossier

Administrative data

Description of key information

Following a precautionary principle, the two constituents of the registered substance (i.e. the two isoforms alpha- and beta-santalols) – often not differentiated in reports – are considered as established contact allergen in animals and humans.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
This report summarizes safety data relevant to the risk assessment of the use of some cyclic and non-cyclic terpene alcohols as fragrance ingredients.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Studies performed before the adoption of the LLNA test method
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route:
other: not specified
Vehicle:
not specified
Concentration / amount:
10 %
Day(s)/duration:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
other: not specified
Vehicle:
not specified
Concentration / amount:
10 %
Day(s)/duration:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
not specified
Details on study design:
not specified
Challenge controls:
Not included.
Positive control substance(s):
yes
Remarks:
Several substances were tested in parallel. Alpha-hexyl cinnamic aldehyde results were included in this ESR as it is one of the preferred positive control substance for GPMT tests.
Positive control results:
See Results table
Key result
Reading:
1st reading
Group:
test chemical
Dose level:
10%
No. with + reactions:
64
Total no. in group:
100
Clinical observations:
not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
Mild sensitizer: Category II, 29-64% of animals with + reactions (No. with + reactions & total number in group not reported))
Key result
Reading:
1st reading
Group:
positive control
Dose level:
10%
No. with + reactions:
80
Total no. in group:
100
Remarks on result:
positive indication of skin sensitisation
Remarks:
Strong sensitizer: Category IV, 65-80% of animals with + reactions (No. with + reactions & total number in group not reported))
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Santalol was allergenic in animals.
Executive summary:

Santalol was reported to be positive in a guinea-pig maximisation test when tested at 10 %.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A RIFM review is available for santalol (CAS #11031-45-1). This review covers both constituents of the registered substance (i.e. the two isoforms alpha- and beta-santalols).

 

The human patch tests are summarized in the following table:

 

Method

Concentration

Results

 

References

Reactions

Incidence (%)

Patch test

2% in petrolatum

47/3123

1.50

Utsumi et al. (1992)

Patch test

5% in petrolatum

1/106

0.94

Sugai (1996)

Patch test

2% in petrolatum

2/133

1.50

Nagareda et al. (1992)

Patch test

2% in petrolatum

3/237

 

1.27

Hashimoto (1990)

Patch test

2% in petrolatum

1/141

0.0071

Nagareda et al. (1996)

Patch test

1% in petrolatum

1/327

0.31

Sugai (1980)

2% in petrolatum

2/327

0.611

 

10% in petrolatum

5/327

1.53

 

Patch test

5% in petrolatum

2/178

1.1

Larsen et al. (2001)

Patch test

10% in petrolatum

7/123

5.7

Hayakawa et al. (1983)

Patch test

2% in petrolatum

37/1244

3

Sugai (1982)

Patch test

N/A

11/716

1.5

Sugai (1986)

Patch test

0.05–0.5% in cream base or ethanol (sample 1)

15/427

3.52

Takenaka et al. (1986)

Patch test

0.05–0.5% in cream base or ethanol (sample 2)

3/214

1.41

Takenaka et al. (1986)

  

- Between April 1979 to August 1990, a total of 3123 male and female patients were patch tested with 2% santalol (a or b not specified) in petrolatum. Reactions were observed in 47/3123 (1.5%) of the patients. The incidence of positive reactions from 1979 to 1990 was 1.5% (Utsumi et al., 1992). This study is summarized in the dossier / Section 7.10.4 [RIFM Panel, 2008].

- During the year 1994, patch testing was conducted in Japan on 106 patients with suspected contact dermatitis, using cosmetic and toiletries ingredients. One (1/106) patient reacted to 5% santalol in petrolatum (Sugai, 1996).

- Nagareda et al. (1992) reported that there were 2 reactions to 2% santalol in petrolatum when patch tests were conducted on 133 cosmetic dermatitis patients from September 1990 to August 1991. Patch tests were conducted using Finn Chambers_ and Scanpore_ tape.

- From September, 1988 to August, 1989 patch tests were conducted on 237 patients using cosmetic ingredients. Three (3/237) patients reacted to santalol at 2% concentration in petrolatum (Hashimoto, 1990).

- During 1992–1993, 2% santalol in petrolatum was patch tested in 141 patients. Reactions were observed in 1/141 or 0.71% of the patients (Nagareda et al., 1996).

- The MJCDRG (Mid-Japan Contact Dermatitis Research Group) conducted patch tests using Finn Chambers_ on Scanpore_ tape on 327 patients at 12 different institutes with santalol at 1, 2, and 10% concentration in petrolatum. Reactions were observed in 1/327, 2/327 and 5/327 patients, respectively (Sugai, 1980).

- In a multicenter study, 178 volunteers with proven sensitization to fragrance materials were patch tested over a 3- month period in eight different centers around the world. Reactions were observed in 1.1% of (2/178) the patients patch tested with 5% a-santalol and b-santalol in petrolatum (Larsen et al., 2001).

- From 1977 to 1982, a total of 123 patients were patch tested. Of these volunteers, seven reacted positively to 10% santalol in petrolatum (Hayakawa et al., 1983).

- From 1973 to 1981, a total of 1244 patients were patch test with 2% santalol in petrolatum. Thirty-seven (3%) pa-tients reacted positively, further details in foreign language (Sugai, 1982).

- The incidence of positive reactions in a Standard Test Series (which included santalol) conducted between 1981 and 1983 were reported. A total of 716 patients were tested to santalol (a or b not specified). Reactions were observed in 11/716 (1.5%). No further details have been reported (Sugai, 1986).

- Closed patch tests were conducted with 0.05–0.5% santalol (specified as santalol 1) in a base cream or in 99% ethanol. Patches consisted of a piece of 1 cm2 lint with a 2 cm2 cellophane disc placed on the lint and then covered with a 4 cm2 plaster. Patches were applied to the back, the forearm, and the inside of the upper arm for 24–48 h. Reactions were observed in 15 patients and questionable reactions were observed in 10 patients out of the total 427 participating. A second sample of santalol (specified as santalol 2) was tested on 214 patients. Reactions were observed in 3 patients and questionable reactions were observed in 6 patients (Takenaka et al., 1986).

 

Additionally, Santalol was allergenic in animals (Maximisation test in guinea-pigs) when tested at 10% for both induction and challenge. This study is summarized in the dossier [RIFM panel, 2008].

Following a precautionary principle, both isoforms – often not differentiated in reports – are considered as established contact allergen in animals and humans.

Reference:

A toxicologic and dermatologic assessment of cyclic and non-cyclic terpene alcohols when used as fragrance ingredients. The RIFM EXPERT Panel, Belsito et al. Food and Chemical Toxicology 46 (2008) S1 -S71.

 

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

Self-classification:

Based on the overall weight-of-evidence, the registered substance is classified as Skin Sens. 1B, H317 (May cause an allergic skin reaction) according to the CLP and the GHS.