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Skin sensitisation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
Alcohols, C9-11-branched and linear
EC Number:
288-284-4
EC Name:
Alcohols, C9-11-branched and linear
Cas Number:
85711-26-8
Molecular formula:
C9H20O, C10H22O and C11H24O
IUPAC Name:
Alcohols, C9-11-branched and linear
Constituent 2
Reference substance name:
C9-11 alcohols
IUPAC Name:
C9-11 alcohols
Test material form:
liquid

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
other: absolute ethanol
Concentration / amount:
Induction and challenge: 1.01%
Challenge
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)

Results and discussion

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.

In vivo (non-LLNA)

Resultsopen allclose all
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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.