Undecan-1-ol

Endpoint summary

Description of key information

Weight of evidence across category suggests that undecanol is not sensitizing to skin. A read across from decan-1-ol has been provided to support this notion (Sharp 1978).

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:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonable reporting of a modified Draize test, result reporting limited. Test sample not characterised.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Modified Draize skin sensitisation test in guinea pigs, involving induction by four simultaneous intradermal injections followed by challenge 14 days later at two sites, by intradermal injection and by open topical application.

GLP compliance:

not specified

Type of study:

other: modified Draize 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 document attached to endpoint study record Clarke & Coombs 1978.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: approximately 350 g
- Housing: wire mesh cages, two animals (same sex) per cage
- Diet (e.g. ad libitum): pelleted guinea pig diet, cabbage and hay ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
No data

IN-LIFE DATES: no data

Route:

intradermal

Vehicle:

no data

Concentration / amount:

Concentrations used for induction: Based on a primary irritation screen the concentration used was 2.5 times the injection challenge concentration (the concentration giving slight barely perceptible irritation with no oedema), 1.9%.
Concentrations used for challenge: 0.75% intradermally and 10% topically

Route:

intradermal and epicutaneous

Vehicle:

no data

Concentration / amount:

Concentrations used for induction: Based on a primary irritation screen the concentration used was 2.5 times the injection challenge concentration (the concentration giving slight barely perceptible irritation with no oedema), 1.9%.
Concentrations used for challenge: 0.75% intradermally and 10% topically

No. of animals per dose:

10 (6 of one sex and 4 of the other)

Details on study design:

RANGE FINDING TESTS: In the preliminary irritation test to determine the injection challenge concentration (ICC), four animals of a single sex were injected intradermally on shaved flanks with 0.1 ml aliquots of a range of concentrations of test material ¿in a suitable solvent¿. Reactions were examined for size, erythema and oedema after 24 hours, and the concentration resulting in slight but perceptible irritation in the absence of oedema was selected as the ICC.

The same method was used for the topical range-finding test, except solutions were applied dermally. The application challenge concentration (ACC) was the highest concentration causing no irritation.

RESULTS OF PILOT STUDY: 1.9%, 0.75% and 10% solutions were chosen for the  intradermal induction, intradermal challenge and topical challenge
respectively

MAIN STUDY
A. INDUCTION EXPOSURE (intradermal)
- No. of exposures: one
- Exposure period: not relevant
- Test groups: one
- Control group: no control group
- Site: Four sites which overlie the two auxilliary and two inguinal lymph nodes
- Frequency of applications: single 0.1 ml application to each site
- Duration: not relevant
- Concentrations: 1.9% (2.5 times the ICC)

B. CHALLENGE EXPOSURE (intradermal)
- No. of exposures: one 0.1 ml application
- Day(s) of challenge: Fourteen days after induction
- Exposure period: Not relevant
- Test groups: one
- Control group: no (only on final challenge)
- Site: flank
- Concentrations: 0.75% (ICC)
- Evaluation (hr after challenge): 24

B. CHALLENGE EXPOSURE (open epicutaneous)
- No. of exposures: one 0.1 ml application
- Day(s) of challenge: Fourteen days after induction
- Exposure period: Not relevant
- Test groups: one
- Control group: no (only on final challenge)
- Site: flank
- Concentrations: 10% (ACC)
- Evaluation (hr after challenge): 24

OTHER:
- Induction and challenge procedures were repeated (after an unspecified time period)
- Hair was shaved from both flanks with Oster animal clippers (size 40 blades) before application of test material.
- Reactions were examined under a Philips colour-matching unit with three Philips 40W Actinic Blue 05 fluorescent tubes and three Philips 40W White 35 fluorescent tubes.
- Each injection reaction was given a total score based on size (¿2 largest diameters¿), erythema and oedema. A reaction was considered positive if its total score was ¿significantly greater¿ than the average total score for control reactions. Topical application reactions were ¿scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls¿.

Challenge controls:

4 animals of the same [unspecified] sex were treated intradermally on one flank and epicutaneously on the other after the final challenge

Positive control substance(s):

not specified

Remarks:

series of compounds tested, some positive for skin sensitisation

Positive control results:

No positive control included, but a series of compounds was tested in the study, some of which were positive for skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.75% intradermal; 10% topical

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no data

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.75% intradermal; 10% topical. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no data.

Reading:

rechallenge

Group:

test chemical

Dose level:

0.75% intradermal; 10% topical

Total no. in group:

10

Clinical observations:

no data; number with reactions unspecified

Remarks on result:

other: Reading: rechallenge. Group: test group. Dose level: 0.75% intradermal; 10% topical. Total no. in groups: 10.0. Clinical observations: no data; number with reactions unspecified.

RESULTS OF TEST
- Sensitisation reaction: No sensitisation following the original induction procedure. Individual animal data not reported. Sensitisation was reported

after a second induction series however the actual number of  animals responding was not reported.
- Rechallenge: Sensitisation reported  on challenge and/or rechallenge following a second induction procedure (no further details regarding number of animals,etc).

Interpretation of results:

study cannot be used for classification

Conclusions:

In a reliable study, conducted by a non-adjuvant procedure (modified Draize), decanol produced a weak sensitisation reaction in guinea pigs only after two sets of induction injections and following topical and/or intradermal challenge. However, no specific details regarding the number of animals affected were reported. On the basis of the study reporting, it is not possible to determine whether or not decan-1-ol is sensitising by skin contact.

Executive summary:

In a reliable study, conducted by a non-adjuvant procedure (modified Draize), decanol produced a weak sensitisation reaction in guinea pigs only after two sets of induction injections and following topical and/or intradermal challenge. However, no specific details regarding the number of animals affected were reported. The significance of this single weakly positive result is very limited on the basis that the result was obtained in a non-standard test assay applying a material of unknown composition and origin. The weight of the evidence indicates that this category does not have a skin sensitisation potential in guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The read across from decan-1 -ol and weight of evidence across category is further supported by a reliability 4 study in human which finds undecanol to not be sensitising to skin (Opdyke 1973).

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 weight of evidence across category and a read across from 1 -hexanol, undecanol is concluded to not be sensitising to skin.