Registration Dossier

Administrative data

Description of key information

The key skin sensitisation study, conducted according to an appropriate OECD test guideline and in compliance with GLP, reported the test substance to be not sensitising to skin (Drug and Safety Testing Center, 1997).

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:
19-Jun-1997 to 04-Sep-1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method. Furthermore, the LLNA test method is not considered to be suitable for fatty alcohols. Please refer to the attached document for further details.

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC Co.
- Age at study initiation: 5 weeks
- Weight at study initiation: 304 to 355 g
- Housing: 5/cage; aluminium cages with stainless steel wire mesh floors (350 x 400 x 200 mm)
- Diet (e.g. ad libitum): standard pelleted guinea pig diet (RC-4), ad libitum
- Water (e.g. ad libitum): tap water 5 um-filtered, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +- 2
- Humidity (%): 50 +- 10
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 24-Jun-1997 To: 04-Sep-1997
Route:
intradermal and epicutaneous
Vehicle:
other: liquid paraffin
Concentration / amount:
3 and 6% intracutaneous induction, 50% epicutaneous induction; 3 and 10% epicutaneous challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
3 and 6% intracutaneous induction, 50% epicutaneous induction; 3 and 10% epicutaneous challenge
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING TESTS:
- 8 females
- concentrations for intracutaneous application: 10, 5, 3, 1, 0.3, 0.1, 0% in liquid paraffin
- concentrations for occluded epicutaneous application (presumably 7 days later): undiluted, 30 and 10% in liquid paraffin
- evaluated for skin irritation at 24, 48 and 72 hours after intracutaneous application
- evaluated for skin irritation at 3, 24 and 48 hours after epicutaneous application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2, intracutaneous and occluded epicutaneous
- Exposure period: epicutaneous induction 7 days after intracutaneous induction; epicutaneous challenge 21 days after intracutaneous induction
- Test groups: 10 females
- Control group: 5 females
- Site: intracutaneous induction in the shaved skin area (~ 4 x 6 cm), symmetrically on both sides of the midline in the scapular region, test animals received (a), (b) and (c), controls received (a), (d) and (a); epicutaneous induction at initially exposed skin site shaved again, test animals received (e), control animals received (d)
- Frequency of applications: epicutaneous induction 7 days after intracutaneous induction
- Duration: epicutaneous induction 48 hours
- Concentrations: (a) 1:1 water-in-oil emulstion of Freunds complete adjuvant (FCA) and physiological saline, (b) test material at 3% in liquid paraffin, (c) 1:1 emulsion of test material at 6% in FCA and physiological saline, (d) liquid paraffin, (e) 0.2 ml of test substance at 50% in liquid paraffin

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21 days after intracutaneous induction
- Exposure period: 24 hours occlusive
- Test groups: 10 females
- Control group: 5 females
- Site: flank, clipped and shaved
- Concentrations: (f) 0.1 ml test substance at 10, 3 and 0% in liquid paraffin
- Evaluation (hr after challenge): 24 and 48 hours after removal of patches

OTHER:
- General condition
- Body weight
- Rechallenge: not required
Challenge controls:
Yes
Positive control substance(s):
yes
Remarks:
2,4-dinitrochlorobenzene and formalin, not concurrent, results from 12 tests at same testing facility
Positive control results:
Evidence presented over a relevant time period that the strain of guinea pig did respond to known sensitisers
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenge: 0, 3 and 10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation

RESULTS OF RANGE FINDING TEST:

Following intradermal injection significant skin irritation was seen at concentrations of 5 and 10% persisting for 72 hours. The 3% concentration showed evidence of irritation at 24 hours only. Following topical application the undiluted material was irritant up to 48 hours, 2/4 guineapigs showed irritation at 10% while there was  no evidence of irritation with the 3% concentration.

RESULTS OF TEST
- Rechallenge: Not required.

Interpretation of results:
GHS criteria not met
Conclusions:
In a reliable study, conducted to OECD guideline 406, Kalcol 2098 was not a skin sensitiser in guinea pigs. The study was performed in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The test material was tested for sensitisation potential in a valid study, conducted according to OECD TG 406 and in compliance with GLP. The test material was diluted in liquid paraffin and concentrations of 3 and 6% were used for intracutaneous induction, 50% for epicutaneous induction, and 3 and 10% for epicutaneous challenge. 10 test and 5 control animals were used in the study.

Following induction, challenge was performed where the test material was applied for guidnea pig skin for 24 hours under occlusive dressing. Skin reactions and sensitisation potential were assessed at 24 and 48 hours after patch removal.

Following intradermal injection significant skin irritation was seen at concentrations of 5 and 10% persisting for 72 hours. The 3% concentration showed evidence of irritation at 24 hours only. Following topical application the undiluted material was irritant up to 48 hours, 2/4 guineapigs showed irritation at 10% while there was no evidence of irritation with the 3% concentration. No skin reactions were observed in any of the test or control animals at challenge.

Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

There is evidence throughout the carbon number range C6-C24 that long chain alcohols are not sensitising; this conclusion does not vary with carbon number within the Category: read-across substances are chosen based on carbon chain length and similarity of physicochemical properties.

A mouse local lymph node assays (LLNA) performed with Alcohols C14-15 branched and linear and with Alcohols C16-17 branched and linear was positive, although this study, which has significant deficiencies in terms of methodology and presentation of results, may have been confounded by skin irritation (House 2000). The LLNA studies pre-date the guideline, OECD TG 429, which indicates that for certain classes of substances, the LLNA may give false positives, and refers to Basketter et al (2009). This paper presents information on two fatty alcohols, and concludes that the fatty alcohols are not sensitisers, and may give a true false positive in the local lymph node assay. For such substances, use of the guinea pig maximisation assay is recommended. Data from guinea pig maximisation assays are available for a number of constituents of the substance and for multi-constituent substances with similar composition; the majority of these studies gave clear negative results. Therefore no classification is proposed for sensitisation, and the Category conclusion is that the members of the C6-24 alcohols category are not sensiters.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data for dodecan-1-ol, no classification for sensitisation is required according to Regulation (EC) No 1272/2008.