Registration Dossier

Administrative data

Description of key information

The key study for skin sensitisation, conducted according to OECD TG 406, and in compliance with GLP, reports tetradecan-1-ol to have no sensitising potential to skin ( Drug and Safety Testing Center Co, 1997; rel 1).

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, Shizuoka
- Age at study initiation: 5 weeks
- Weight at study initiation: 313-337 g
- Housing: animals were housed in aluminium cages with stainless steel wire mesh floors (350 mm x 400 mm x 200 mm, Natsume Seisakusyo Co., Tokyo); 5 animals/cage.
- Diet (e.g. ad libitum): standard pelleted diet for guinea-pigs (RC-4; Oriental Yeast Co.) ad libitum
- Water (e.g. ad libitum): filtered tap water ad libitum
- Acclimation period: 7 days

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

IN-LIFE DATES: 19-Jun-1997 to 04-Sep-1997
Route:
intradermal and epicutaneous
Vehicle:
other: liquid paraffin
Concentration / amount:
Induction: 5% (w/w) intracutaneous, 50% (w/w) epicutaneous occlusive
Challenge: 3% (w/w) and 10% (w/w)
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
Induction: 5% (w/w) intracutaneous, 50% (w/w) epicutaneous occlusive
Challenge: 3% (w/w) and 10% (w/w)
No. of animals per dose:
10 test animals, 5 control animals
Details on study design:
RANGE FINDING STUDY: A preliminary test was performed to assess primary skin irritation using 8 female guinea-pigs. Test substance was administered to four animals by intradermal injection (10%, 5%, 3%, 1%, 0.3% and 0.1% w/w) and to four animals by 24-hr occluded patch. The number of animals showing skin irritation was recorded at 24, 48 and 72 hrs after intradermal treatment and at 3, 24 and 48 hrs after occluded patch testing. The results of this test were used to determine the doses for intradermal injection, topical induction and topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 - intracutaneous, followed by epicutaneous 7 days later
- Exposure period: 21 days between initial induction and challenge
- Test groups: 10 females
- Control group: 5 females
- Site: intracutaneous - intradermal injections were performed in the shaved skin area on both sides of the midline in the scapular region; epicutaneous - occlusive patches were applied to the previously treated areas
- Frequency of applications: intracutaneous induction followed by epicutaneous induction 1 week later
- Duration: epicutaneous induction - 48 hrs
- Concentrations: 5% intracutaneous, 50% epicutaneous

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2
- Exposure period: 24 hrs
- Test groups: 10 females
- Control group: 5 females
- Site: flank
- Concentrations: 3%, 10 % (w/w)
- Evaluation (hr after challenge): 24, 48 hrs

OTHER:
Grading system used for evaluation of patch test results (Magnusson and Kligman) : 0 = no visible change, 1 = discrete or patch erythema; 2 = moderate and confluent erythema; 3 = intense erythema and swelling.

MAIN STUDY
Induction:
(Day 0) Intradermal injections of 0.1ml of each of following: (a) 1:1 (v/v) emulsion of Freund’s complete adjuvant (FCA) and physiological saline, (b) 5% (w/w) of the test substance in liquid paraffin, and 1:1 (v/v) emulsion of 10% (w/w) test substance in FCA and physiological saline.
(Day 7) Occluded patches of 0.2 ml 50% (w/w) of the test substance in liquid paraffin were applied for 48 hrs.
Challenge:
(Day 21) Occluded patches of 0.1 ml of each of the 10%, 3% (w/w) of the test substance in liquid paraffin and liquid paraffin alone were applied for 24 hrs.
Challenge controls:
Five female animals were administered intradermally: 0.1 ml of liquid paraffin and 0.1 ml of an emulsion of Freund’s complete adjuvant (FCA) and physiological saline. Seven days later an occluded patch of liquid paraffin was applied for 48 hrs. At the challenge exposure, occluded patches of paraffin were applied to the animals flanks for 24 hrs.
Positive control substance(s):
yes
Remarks:
DNCB and formalin, not concurrent
Positive control results:
Evidence presented over a relevant time period that the strain of guinea pig did respond to known sensitisers.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
3% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test .
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
3% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test. .
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test .

RESULTS OF RANGE FINDING STUDY:

Following intradermal injection, skin irritation was seen at concentrations of 10% and 5% persisting for 72 hours

but less marked at the lower concentration. The 3% concentration showed evidence of irritation at 24 hours in oneanimal only. Lower concentrations from 0.1 -1% showed no irritation. Following topical application slight irritation was seen in 2/4 animals at 50% only.

TEST: There was no evidence of sensitisation in any of the test or control animals at either challenge concentration

 

Table 1. Summary of the delayed contact hypersensitivity study of KALCOL 4098 in female guinea-pigs

 

Group

Number of animals showing positive reaction/Total number of animals

24 hrs after challenge

48 hrs after challenge

10%

3%

vehicle

10%

3%

vehicle

Test

0/10

0/10

0/10

0/10

0/10

0/10

Control

0/5

0/5

0/5

0/5

0/5

0/5

Interpretation of results:
GHS criteria not met
Conclusions:
Kalcol 4098 showed no evidence of being a skin sensitizer when tested using the Guinea pig maximization test in a reliable study conducted in accordance with OECD Guidelines 406. The study was GLP compliant. The study is a read across from tetradecanol (CAS 112-72-1).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The key study was the most recent and high reliability study available. In the study, diluted test material in liquid paraffin was tested in 10 guinea pigs. Control group consisted of 5 animals ( Drug and Safety Testing Center Co, 1997).

At induction phase, 0.1 ml of 5% (w/w) of test material in liquid paraffin was applied intracutaneously as intradermal injection. 7 days later, 0.2 ml of 50 % (w/w) was applied epicutaneously to the test area and kept in contact to the skin under occlusive dressing for 48 hours.

At challenge phase (21 days after induction), 0.1 ml of 3% and 10 % (w/w) of test material in liquid paraffin were applied onto the skin of the test animals and kept in contact under occlusive dressing fro 24 hours.

Skin reaction scores were evaluated at 24 and 48 hours after challenge.

No skin reactions were noted at 24 and 48 hours observations. The test material was reported to be not sensitising under the conditions of the study. The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

A reliability 4 supporting study in human supports the findings of the key study (Opdyke, 1975).

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 information, tetradecan-1 -ol does not require classification for skin sensitisation according to Regulation (EC) No 1272/2008.