Alcohols, C9-11-branched and linear

Endpoint summary

Description of key information

In the key in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 and in compliance with GLP, Alcohols, C9-11-branched and linear (1% in ethanol) was not sensitising to the skin of guinea pigs when tested using the Buehler non-adjuvant method (Shell, 1981c).

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:

02 March 1981 to 03 April 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

(only 10 animals/group; absolute ethanol used as vehicle; possibly the highest non-irritant concentration may not have been used; positive control response ambiguous)

GLP compliance:

yes

Remarks:

Deviation from GLP regulations: No retain was obtained of the vehicle control, absolute ethanol (USP)

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/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/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Camm Research Laboratories, Wayne, New Jersey, USA
- Age at study initiation: no data
- Weight at study initiation: 529 - 561 g (group means)
- Housing: Stainless steel cages, 5 animals per cage
- Diet (e.g. ad libitum): Purina Lab Guinea Pig Chow 5025, ad libitum
- Water (e.g. ad libitum): Tap water, Edstrom automatic watering system, ad libitum
- Acclimation period: at least 13 days; up to 20 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 22.5 (range 21.7 - 23.9)
- Humidity (%): average 49.6 (range 30-60)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route:

epicutaneous, occlusive

Vehicle:

other: absolute ethanol

Concentration / amount:

Induction and challenge: 1.01%

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: absolute ethanol

Concentration / amount:

Induction and challenge: 1.01%

No. of animals per dose:

10 (5 males, 5 females); applies to all groups

Details on study design:

RANGE FINDING TESTS:
1 animal/sex was treated epicutaneously (at two sites) with 1, 50 or 100% Neodol 91 (where applicable dissolved in absolute ethanol) under occlusion for 6 hours. Only the 1% solution did not elicit a reaction indicative of irritation.

MAIN STUDY - Non-adjuvant Buehler test
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 3 weeks
- Test groups: 1
- Control group: 2 (vehicle and positive controls)
- Site: back/trunk
- Frequency of applications: one day/week, on 3 consecutive weeks
- Duration: 6 hours
- Concentrations: 1.01 % (volume 0.5 ml)
- Reactions were scored approximately 24 and 48 hours after treatment (Draize grading system)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28 (i.e. 2 weeks after final induction)
- Exposure period: 6 hours
- Test groups: 1
- Control group: 3 (vehicle, positive and irritation controls)
- Site: back/trunk (two patches, on sensitized and virgin application sites)
- Concentrations: 1.01% (volume 0.5 ml)
- Evaluation (hr after challenge): 24 and 48 (Draize grading system)

No rechallenge.

OTHER: Exposure sites were shaved (48 hours) and depilated (24 hours) prior to exposure.

Each treatment involved dispensing the appropriate dose on a 1"x1" gauze pad attached to a 2" wide strip of Blenderm (R) surgical tape (Minnesota mining and Manufacturing, Saint Paul, Minnesota), then applying the patch to the anterior central portion of the back/trunk and securing with Saran wrap (Dow Chemical co., Indianapolis, Indiana). Animals were placed in a stainless steel wire restrained for the six-hour application duration for the first and second applications (for the 3rd and challenge applications, they had outgrown the restrainers and so these were not used; nevertheless the patches and wraps remained in situ). Excess test material was removed with a moistened gauze pad.

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

2,4-Dinitrochlorobenzene (0.1% solution in diethyl ether)

Positive control results:

The positive controls showed a significant response at challenge  with all test sites showing an increased degree of irritation. However, reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

"Barely perceptible" redness at original site (i.e. induction site) in 6/10 animals (indicative of mild irritation); no reactions at challenge site

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1% DNCB

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization.

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.1% DNCB

No. with + reactions:

9

Total no. in group:

9

Clinical observations:

One animal died (not treatment related). Reactions were similar to those seen during induction and so were not unambiguously indicative of sensitization.

Remarks on result:

positive indication of skin sensitisation

RESULTS OF TEST 

There was slight irritation in the  test group during the induction period. The average Draize score was 0.38 at week  1, 0.5 at week 2 and 0.28 at week 3. By week 5 the score was zero (no irritation seen).

Average irritation at challenge for the treated group was 0, positive  controls were 1.55, vehicle controls 0.08 and irritation controls 

 (challenge application only) 0.13.

Interpretation of results:

GHS criteria not met

Conclusions:

In the in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 and in compliance with GLP, Alcohols, C9-11-branched and linear (1% in ethanol) was not sensitising to the skin of guinea pigs when tested using the Buehler non-adjuvant method.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In the in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 and in compliance with GLP, Alcohols, C9-11-branched and linear (1% in ethanol) was not sensitising to the skin of guinea pigs when tested using the Buehler non-adjuvant method (Shell, 1981c).

During epicutaneous induction, the test material was diluted in absolute ethanol to concentration of 1.01 % and applied onto the skin under occlusive dressing for 6 hours. Skin reactions were assessed at 24 and 48 hours post-exposure. The epicutaneous induction was repeated 3 times in three consecutive weeks.

During challenge, which was conducted two weeks after the last induction, the test material was diluted in absolute ethanol to achieve concentration of 1.01 %. The test item was applied onto the skin under occlusive dressing for 6 hours and skin reactions were assessed at 24 and 48 hours post-exposure. No skin reactions were seen in the test group but the guideline requirement for the use of the highest non-irritating concentration may not have been achieved since the next highest concentration tested in the pre-screen, which produced irritation, was 50 %. The positive control gave an ambiguous sensitisation response.

The conclusion of the key study is supported by the in vivo skin sensitisation study for the analogue Alcohols, C9-11. The study was conducted according to a protocol similar to OECD Test Guideline 406, but prior to GLP and concluded Alcohols, C9-11 to be not a skin sensitiser in guinea pigs after a topical challenge with 5% test item (Shell, 1978).  Corn oil was used as the vehicle for the test material and induction applications were 0.1 % intradermal and 10 % occlusive epicutaneous. Challenge application was 5 % occlusive epicutaneous. No skin reactions were seen after challenge.

 

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.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

The test material contains no structural groups suggestive of respiratory sensitisation and, together with the lack of skin sensitising potential, it is unlikely to be a respiratory sensitiser.

Justification for classification or non-classification

Based on the available data, Alcohols C9-11 linear and branched would not be classified as a skin or respiratory sensitiser according to Regulation (EC) No. 1272/2008 . Tests on similar substances included in this category are also supportive of these results, which do not warrant classification for sensitisation under DSD or GHS criteria.