Decan-1-ol

Endpoint summary

Description of key information

The key in vivo skin sensitisation study for decan-1-ol (Eurofins, 2008, Rel1, GLP), conducted according to a protocol similar to OECD Test Guideline 406 and in compliance with GLP, concluded decan-1-ol to be not sensitising to guinea pig skin.

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:

31st of July 2008 to 4th of September 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler 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 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

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Elm Hill Breeding Labs., Chelmsford, MA
- Age at study initiation: young adult
- Weight at study initiation: 357-449g
- Housing: group-housed in suspended stainless steel caging with mesh floors or plastic perforated bottom caging.
- Diet: Pelleted Purina Guinea Pig Chow ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: 4-17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 56-79
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Concentration / amount:

0.4ml of undiluted test material was used for the induction phase.
0.4 ml of a 25% w/w mixture of the test substance in mmineral oil was used for the challenge phase.

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Concentration / amount:

0.4ml of undiluted test material was used for the induction phase.
0.4 ml of a 25% w/w mixture of the test substance in mmineral oil was used for the challenge phase.

No. of animals per dose:

Preliminary irritation group:4
Test group: 10
Naive control group: 10

Details on study design:

INDUCTION PHASE:
Once each week for three weeks, 0.4ml of the undiluted test substance was applied to the left side of each test animal using an occlusive 25 mm Hill Top CHamber. The chambers were secured in place and wrapped with adhesive tape to avoid dislocation of the chambers and to minimize loss of the test substance. After the 6
h exposure period, the chambers were removed and the test sites were gently cleansed with a 3% soap solutionh followed by tap water using a clean paper towel to remove any residual test substance. Approximately 24 and 48 hours after each induction application, readings were made of local reactions (erythema).

CHALLENGE PHASE:
Twenty-seven days after the first induction dose, 0.4 ml of a 25% w/w mixture of the test substance in mineral oil was applied to a naive site on the right side of each animal as a challenge dose, using the procedures described above. These sites were evaluated for a sensitization response (erythema) approximately 24 and 48 hours after the challenge application.

Challenge controls:

In addition to the test animals, 10 guinea pigs from the same shipment were maintained under identical environmental conditions and were treated with mineral highest non irritating concentration of the test substance at challenge only.

Positive control substance(s):

yes

Remarks:

alpha-Hexylcinnamaldehyde technical

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.4 ml, 25% w/w mixture of the test substance in mineral oil

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

very faint erythema (0.5) present in 5 of 20 of the animals (not considered as positive reaction)

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.4 ml, 25% w/w mixture of the test substance in mineral oil

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Very faint erythema (0.5) present in 2 of 20 of the animals (not considered as positive reaction)

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.4 ml, 25% w/w mixtre of the test sbstance in mineral oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Very faint erythema present (0.5) was noted for 1 out of 10 control sites at 24 hours after challenge. Irritation was clear from the test site by 48 hours after challenge.

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.4 ml, 25% w/w mixture of the test substance in mineral oil

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

100% HCA

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

Clear erythema in 4 of 10 animals and very faint erythema present in an additional 4 of 10 animals (not considered as positive reaction)

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

100% HCA

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

Clear erythema in 2 of 10 animals and very faint erythema present in an additional 5 of 10 animals (not considered as positive reaction)

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100% HCA

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Very faint erythema in 1 of 5 animals

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100% HCA

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Very faint to faint erythema was noted for all test sites during the induction phase. Same observation was noted in positive control sites during the induction phase.

Very faint erythema was noted for five of twenty test sites 24 hours after challenge. Similar irritation persisted at two sites through 48 hours.

Very faint erythema was noted for one of ten naive control sites 24 hours after challenge. Irritation was clear from this site by 48 hours.

Four of ten positive control animals exhibited signs of a sensitization response (faint erythema) 24 hours after challenge. Similar indications persisted at two sites through 48 hours.

Very faint erythema was noted for one naive control site 24 hours after challenge. irritation cleared from the affected site by 48 hours.

Based on these findings the test material is not considered to be a contact sensitizer. The positive response observed in the historical positive control validation study with alpha-hexylcinnamaldehyde technical (HCA) validates the test system used in this study.

Interpretation of results:

GHS criteria not met

Conclusions:

The in vivo skin sensitisation study for decan-1-ol, conducted according to a protocol similar to OECD Test Guideline 406 and in compliance with GLP, concluded decan-1-ol to be not sensitising to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The key in vivo skin sensitisation study for decan-1-ol (Eurofins, 2008, Rel1, GLP), conducted according to a protocol similar to OECD Test Guideline 406 and in compliance with GLP, concluded decan-1-ol to be not sensitising to guinea pig skin.

During the induction phase, 0.4 ml of the undiluted decan-1-ol was applied to the left side of each test animal using an occlusive 25 mm Hill Top Chamber. The chambers were secured in place and wrapped with adhesive tape to avoid dislocation of the chambers and to minimize loss of the test substance. After the 6-hour exposure period, the chambers were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water using a clean paper towel to remove any residual test substance. Approximately 24 and 48 hours after each induction application, readings were made of local skin reactions (erythema). The induction was performed once a week for 3 weeks.

During the challenge phase, twenty-seven days after the first induction dose, 0.4 ml of a 25% w/w mixture of decan-1-ol in mineral oil was applied to a naive site on the right side of each animal as a challenge dose, using the procedures described above. These sites were evaluated for skin sensitisation response (erythema) at approximately 24 and 48 hours after the challenge application.

Very faint to faint erythema was noted for all test sites during the induction phase. Same observation was noted in positive control sites during the induction phase.

Very faint erythema was noted for five of twenty test sites at 24 hours after challenge. Similar irritation persisted at two sites through 48 hours. Very faint erythema was noted for one of ten naive control sites at 24 hours after challenge. Irritation was clear from this site by 48 hours.

Four of ten positive control animals exhibited signs of a sensitisation response (faint erythema) at 24 hours after challenge. Similar indications persisted at two sites through 48 hours. Very faint erythema was noted for one naive control site at 24 hours after challenge. Irritation cleared from the affected site by 48 hours.

Based on these findings the test material is not considered to be a contact skin sensitiser. The positive response observed in the historical positive control validation study with alpha-hexylcinnamaldehyde technical (HCA) validates the test system used in this study.

Under the conditions of the key skin sensitisation Buehler study in guinea pigs (Eurofins 2008, rel 1) no skin sensitising effects were reported. In addition, weight of evidence from a reliable modified Draize study in guinea pigs (Sharp, 1978, rel 2) albeit with limited reporting found decan-1-ol to be at most mildly sensitising, however insufficient data were provided to reach a conclusion on sensitisation. Furthermore, weight of evidence from a human skin patch test using decan-1-ol (Opdyke 1973, rel 4) finds the material not to be sensitising by skin contact. A well-conducted skin sensitisation study (Saitama 1997, original study rel 1) using read-across from dodecan-1-ol, reported no sensitising effects under the conditions of the study. 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.

In conclusion decan-1-ol is not considered to be sensitising to skin.

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