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Administrative data

Description of key information

The key skin sensitisiation study for hexadecan-1-ol, conducted according to an appropriate OECD Test Guideline 406 and in compliance with GLP, reports the substance to be not sensitising to guinea pig skin (Safepharm Laboratories, 1996).

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:
weight of evidence
Study period:
11-Mar-1996 to 03-Jun-1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
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:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Ltd., UK
- Age at study initiation: ~8-12 weeks
- Weight at study initiation: 376-454 g
- Housing: singly or in pairs, in solid-floor polypropylene cages furnished with wood flakes
- Diet (e.g. ad libitum): Guinea pig FD1 diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 44-74
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 11-Mar-1996 To: 03-Jun-1996
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 1%
Epicutaneous induction: 50%
Epicutaneous challenge: 25 and 50%
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Intradermal induction: 1%
Epicutaneous induction: 50%
Epicutaneous challenge: 25 and 50%
No. of animals per dose:
10 test, 5 control
Details on study design:
RANGE FINDING TESTS:
Intradermal induction
- 1 animal received 4 x 0.1 ml injections of test material at 1% (w/v)
- erythema assessed at 1, 2, 3 and 7 days after injection
- concentration selected that caused only mild to moderate skin irritation and was well tolerated systemically
Epicutaneous induction
- 2 animals injected with Freund's Complete Adjuvant (FCA) 11 days prior to application of test material at 5, 10, 25 and 50% (w/w)
- clipped flanks, occlusive, 48 hours
- erythema and oedema assessed at 1, 24 and 48 hours after the end of exposure
- concentration selected that caused only mild to moderate dermal irritation
Topical challenge
- 2 animals, test material at 5, 10, 25 and 50% applied to clipped flanks, occlusively for 24 hours (after being treated in the same way as control animals in the main study for the previous 14 days)
- erythema and oedema assessed at 1, 24 and 48 hours after the end of exposure
- highest non-irritant concentration selected

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 simultaneous intradermal injections; followed one week later by epicutaneous application
- Exposure period: single timepoint for intradermal injections; 48 hour epicutaneous application 7 days later
- Test groups: 10 animals
- Control group: 5 animals
- Site: clipped shoulder region, 40 x 60 mm
- Frequency of applications: intradermal induction followed 7 days later by epicutaneous induction
- Duration: single timepoint for intradermal injections; 48 hour epicutaneous application 7 days later
- Concentrations:
- intradermal induction, each 0.1 ml: test animals (a) FCA:water 1:1, (b) 1% (w/v) test material in arachis oil, (c) 1% (w/v) test material in FCA:water 1:1; control animals (a) FCA:water 1:1, (b) arachis oil, (c) 50% w/v arachis oil in FCA:water 1:1
- epicutaneous induction, thick even layer on filter patch 20 x 40 mm: test animals 50% w/w in arcahis oil; control animals, arachis oil; occluded
- Evaluation: erythema and oedema assessed 1 and 24 hours after patch removal

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: epicutaneous challenge on day 21
- Exposure period: 24 hour epicutaneous application
- Test groups: 10 animals
- Control group: 5 animals
- Site: clipped flanks, 50 x 70 mm
- Concentrations: epicutaneous challenge, thick even layer on filter paper patch 20 x 20 mm, 25% and 50%, one to each flank; occluded
- Evaluation (hr after challenge): erythema and oedema assessed 24 and 48 hours after patch removal

OTHER:
- Body weight recorded at start and end of study
- Any other reactions noted when erythema and oedema evaluated
Challenge controls:
5 non-induced animals received challenge applications
Positive control substance(s):
yes
Remarks:
not concurrent, ethyl 4-aminobenzoate, 2,4-dinitrochlorobenzene, neomycin sulphate, 2-mercaptobenzothiazole
Positive control results:
Evidence of reaction of the strain of guinea pigs to known skin sensitisers over an appropriate period was provided.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 and 50% (challenge)
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
other: Evidence of reaction of the strain of guinea pigs to known skin sensitisers over an appropriate period was provided.

RESULTS OF PILOT STUDY: Intradermal. Erythema (grade 2) observed at all injection sites, no systemic toxicity. Tested at 1% only. Topical 

application for induction (48 hour) minimal irritation at 5 and 10%, with 25 and 50% maximum erythema score 2 persisting to 48 hours after removal of patch. Topical application for challenge initial minimal response at 1 hour, no irritation at 24 and 48 hours.

RESULTS OF TEST
- Sensitization reaction: No sensitisation reaction in any of the test or control animals. Response 0/10 test, 0/5 controls.
- Clinical signs: Body weights and weight gain over the observation period were comparable in test and control groups. One animal was killed after 

topical challenge, the reason was not given but this was not considered to affect the results of the test. Well defined - moderate erythema at the 

intradermal injection site 24 hours after induction, well defined erythema at 48 hours. Following topical induction very slight to well defined 

erythema was noted 1 hour after patch removal, very slight erythema observed in 2/10 test animals at 24 hours. No skin reactions following topical 

challenge.
- Rechallenge: Not required.

Interpretation of results:
GHS criteria not met
Conclusions:
In a reliable study, conducted according to OECD guideline 406, Kalcohl 6098 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 key skin sensitisiation study for hexadecan-1-ol, conducted according to an appropriate OECD Test Guideline 406 and in compliance with GLP, reports the substance to be not sensitising to guinea pig skin (Safepharm Laboratories, 1996).

At induction, 3 simultaneous intradermal injections were performed followed by a 48-hour epicutaneous application one week later. The intradermal induction consisted of three 0.1 ml intradermal injections. The 10 test animals received (a) FCA:water 1:1, (b) 1% (w/v) test material in arachis oil, (c) 1% (w/v) test material in FCA:water 1:1; the 5 control animals received (a) FCA:water 1:1, (b) arachis oil, (c) 50% w/v arachis oil in FCA:water 1:1. The epicutaneous induction consisted of the occluded 48-hour dermal application of 50% w/w test substance in arachis oil onto the skin of the 10 test animals and arachis oil onto the skin of the 5 control animals. Erythema and oedema were assessed at 1 and 24 hours after patch removal.

At challenge, the test substance was applied dermally for 24 hours under occluded dressing onto the skin of the 10 test animals and 5 control animals at concentrations of 25% and 50% in arachis oil. Erythema and oedema were assessed at 24 and 48 hours after patch removal. Body weights and weight gain over the observation period were comparable in test and control groups. One animal was killed after  topical challenge, the reason was not given but this was not considered to affect the results of the test. Well-defined to moderate erythema at the  intradermal injection site was noted at 24 hours after induction, well-defined erythema was observed at 48 hours. Following topical induction very slight to well-defined  erythema was noted at 1 hour after patch removal, very slight erythema was observed in 2/10 test animals at 24 hours. No skin reactions were noted following topical  challenge. No sensitisation reactions were noted in any of the test or control animals. Responses were: 0/10 for the test animals and 0/5 for the control animals.

A reliability 2 supporting study is in accordance with the key study, reporting the test substance to be not sensitising (Gloxhuber, 1983; rel 2). The existing key study was selected as key since it was the most recent, high reliability study available.

A full discussion of the Category and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

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 hexadecan-1-ol, no classification is required for sensitisation according to Regulation (EC) No 1272/2008.