Octan-1-ol

Endpoint summary

Description of key information

No high reliability studies for skin sensitisation of octan-1-ol were available. Therefore, key data from the close category member, hexan-1-ol, were read-across due to the similarity of the substances.

In the key in vivo skin sensitisation study, conducted by a non-adjuvant modified Draize test procedure (reliability 2) and prior to GLP, hexan-1-ol was concluded to be not a skin sensitiser in guinea pigs following intradermal and topical challenge after 2 series of induction applications (Sharp, 1978). The study was conducted according to guideline similar to OECD Test Guideline 406.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Reasonable reporting of a modified Draize test, result reporting limited. Test sample not fully characterised. Controls only included at rechallenge. On a related material.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Skin sensitisation test in guinea pigs. Range finding (preliminary irritation) test by intradermal injection and topical application. Sensitisation test with induction by intradermal injection followed by intradermal and topical challenge. Repeated induction and rechallenge if negative results.

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 Buehler/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:

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:

not specified

Concentration / amount:

2.5 times the injection challenge concentration of 0.1%

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

0.1%

Adequacy of challenge:

highest non-irritant concentration

No.:

#1

Route:

epicutaneous, open

Vehicle:

not specified

Concentration / amount:

10%

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Preliminary test: 4 animals
Main test: 10 animals

Details on study design:

- Preliminary test: 4 animals were injected intradermally in their shaved flanks with 0.1 ml of hexan-1-ol in appropriate solvent (not specified) at different concentrations (not specified). The reactions were examined for size, erythema and oedema at 24 hours post injection and the concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration. In addition to intradermal injection, topical application of 0.1 ml of hexan-1-ol at different concentrations (not specified) in appropriate solvent (not specified) were applied on the shaved flanks of 4 guinea pigs. The erythema skin reactions were examined at 24 hours post application and the highest concentration, which caused no irritation, was selected as the application challenge concentration.

For the main skin sensitisation study, 0.25%, 0.1% and 10% solutions were the chosen concentrations for the intradermal induction, intradermal challenge and topical challenge, respectively, to be tested onto the skin of 10 guinea pigs per dose. No positive control included, but a series of compounds was tested in the study, some of which were positive for skin sensitisation.

Induction and challenge: During the induction phase, 0.1 ml of hexan-1-ol at 0.25% concentration (2.5 times the injection challenge concentration of 0.1%) were injected intradermally to 10 guinea pigs at 4 sites which overlie the 2 auxiliary and 2 inguinal lymph nodes. Two weeks later, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml of hexan-1-ol at the respective injection challenge concentration of 0.1& and application challenge concentration of 10%. Skin reactions were assessed at 24 hours post challenge and apparent sensitisation reactions confirmed 7 days later by a second challenge with controls included. If no skin sensitisation was observed following the first challenge, the induction and challenge procedures were repeated, but with confirmatory challenge controls. The challenge controls were not induced but treated in a similar way as test animals at challenge.

Challenge controls:

Not used at first challenge. Untreated challenge controls used at follow-up challenge applications.

Positive control substance(s):

not specified

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

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1% intradermal; 10% topical

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Individual animal data were not presented.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1% intradermal; 10% topical

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Individual animal data were not presented.

Group:

positive control

Remarks on result:

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

Group:

negative control

Remarks on result:

other: Individual animal data were not presented.

Individual animal data were not presented.

Interpretation of results:

GHS criteria not met

Conclusions:

In an in vivo skin sensitisation study, conducted by a non-adjuvant modified Draize test procedure (reliability 2) and prior to GLP, hexan-1-ol was concluded to be not a skin sensitiser in guinea pigs following intradermal and topical challenge after 2 series of induction applications.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No high reliability studies for skin sensitisation of octan-1-ol were available. Therefore, key data from the close category member, hexan-1-ol, were read-across due to the similarity of the substances.

The key in vivo skin sensitisation study for hexan-1-ol was conducted by a non-adjuvant modified Draize test procedure (reliability 2) and prior to GLP (Sharp, 1978). The study was conducted according to guideline similar to OECD Test Guideline 406.

During the preliminary test, 4 animals were injected intradermally in their shaved flanks with 0.1 ml of hexan-1-ol in appropriate solvent (not specified) at different concentrations (not specified). The reactions were examined for size, erythema and oedema at 24 hours post injection and the concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration.

In addition to intradermal injection, topical application of 0.1 ml of hexan-1-ol at different concentrations (not specified) in appropriate solvent (not specified) were applied on the shaved flanks of 4 guinea pigs. The erythema skin reactions were examined at 24 hours post application and the highest concentration, which caused no irritation, was selected as the application challenge concentration.

For the main skin sensitisation study, 0.25%, 0.1% and 10% solutions were the chosen concentrations for the intradermal induction, intradermal challenge and topical challenge, respectively, to be tested onto the skin of 10 guinea pigs per dose. No positive control included, but a series of compounds was tested in the study, some of which were positive for skin sensitisation.

During the induction phase, 0.1 ml of hexan-1-ol at 0.25% concentration (2.5 times the injection challenge concentration of 0.1%) were injected intradermally to 10 guinea pigs at 4 sites which overlie the 2 auxiliary and 2 inguinal lymph nodes. Two weeks later, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml of hexan-1-ol at the respective injection challenge concentration of 0.1& and application challenge concentration of 10%. Skin reactions were assessed at 24 hours post challenge and apparent sensitisation reactions confirmed 7 days later by a second challenge with controls included. If no skin sensitisation was observed following the first challenge, the induction and challenge procedures were repeated, but with confirmatory challenge controls. The challenge controls were not induced but treated in a similar way as test animals at challenge.

The results from the first challenge were negative, therefore a repeat set of induction applications was carried out followed by challenge at 14 days and rechallenge (with controls) 7 days later. 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.

No signs of erythema or oedema were observed at challenge and rechallange in any of the test animals for hexan-1-ol. Hexan-1-ol was concluded to be not sensitising to skin.

In addition, a reliability 4 supporting study in humans was available which found octan-1-ol to be not sensitising to skin in humans (Opdyke, 1973).

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 sensitisers.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available read-across information from the structurally similar substance hexan-1-ol, it is concluded that octan-1-ol does not require classification for skin sensitisation according to Regulation (EC) No 1272/2008.