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Description of key information

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:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The OECD Test Guideline for LLNA was not available at time of study implementation. Existing data from GPMT study scientifically adequate.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Stolzenseeweg 32, 88353 Kissleg, Germany
- Age at study initiation: young adult
- Weight at study initiation: 345-366 g
- Housing: Macrolon type-III cages with 2-3 animals/cage
- Diet: Purina Base - Lap gr diet for rabbit (Agribrands Europe Hungary PLC, H-5300 Karcag, Madarasi Road, Hungary), ad libitum; suitable for guinea pigs and also used by the breeder
- Water: tap water with ascorbic acid 0.5 mg/mL, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Air changes: 15-20 air changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 30-Sep-2009 To: 25-Oct-2009
Route:
intradermal and epicutaneous
Vehicle:
other: Sesame oil
Concentration / amount:
Intradermal induction exposure: 5 %
Dermal induction exposure: 100 %
Challenge exposure: 25 % (with 12.5 % applied on the other flank of each animal as safeguard dose)
Route:
epicutaneous, occlusive
Vehicle:
other: Sesame oil
Concentration / amount:
Intradermal induction exposure: 5 %
Dermal induction exposure: 100 %
Challenge exposure: 25 % (with 12.5 % applied on the other flank of each animal as safeguard dose)
No. of animals per dose:
10 test animals, 5 control animals
Details on study design:
RANGE FINDING TESTS:
For the intra-dermal application, 0.1 mL of formulated test item was injected at concentrations of 0.01, 0.1, 1.0, 5.0, 10 and 25 % (all w/v) into the hair free skin. The treated areas were covered for 24 hours with porous gauze fastened with "Clinipore-silk". For the dermal application, animals pre-treated with Freund’s Adjuvant were used. On day 1, each animal received 2 injections of 0.1 mL Freund's Adjuvant mixed with physiological saline (1:1 v/v). On day 8, 0.5 mL per concentration (25, 50, 75 (all w/v) and 100 %) was applied onto hair free skin of the animals. A closed patch exposure was applied by means of an occlusive bandage

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal
- No. of exposures: 1
- Exposure time: day 1 (6 injections/animal)
- Test groups: 1
- Control group: 1
- Site: dorsal, flank
- Frequency of applications: single application
- Concentration: 5 % (w/v)

Dermal
- No. of exposures: 1
- Exposure time and duration: day 8 (closed patch), for 48 hours
- Site: dorsal, flank
- Frequency of applications: single application
- Concentration: 100 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: day 22
- Exposure period: 24 hours
- Test groups: 1
- Control group: 1
- Site: dorsal, flank
- Concentration: 25 % (with 12.5 % applied on the other flank of each test animal as safeguard dose)
- Evaluation: Magnusson and Kligman grading scale

The sensitivity and reliability of the experimental procedure was assessed by use of the reference item 2 -Mercaptobenzothiazole under LAB Research Ltd. study number 09/141 -104T (29-Jun-2009 to 24-Jul-2009).
Challenge controls:
Control animals were treated similarly to test animals, except that during the induction phase the test item was omitted.
Positive control substance(s):
not required
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
25 %
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
25 %
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
peeling of the skin in 6/10 animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25 %. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: peeling of the skin in 6/10 animals.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5 % (safeguard dose)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 12.5 % (safeguard dose) . No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
12.5 % (safeguard dose)
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 12.5 % (safeguard dose) . No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
12.5 % (safeguard dose)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 12.5 % (safeguard dose) . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
12.5 % (safeguard dose)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 12.5 % (safeguard dose) . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:

In a dermal sensitisation study (Török-Batho, 2010) with 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues (≥98 %) in sesame oil, young adult Hartley guinea pigs (test group: 10 males, control group: 5 males) were tested using the guinea pig maximisation test of Magnusson and Kligman. Challenge with the test item resulted in a mean score of 0.70 (7/10) and 0.20 (2/10) at the 48 and 72 hour observations (24 and 48 hours after patch removal), respectively. The net response value was 70 %, as barely perceptible erythema at the first observation. However, the net response value at the second observation was only 20 %. No signs of skin reaction were noted following treatment with the safeguard concentration (corresponding to 50 % of the challenge concentration). Since for an immune response it would be expected that under the conditions of this study many animals treated with the challenge dose would have a reaction persisting to the second observation, there would be at least some animals with a grade 2 or 3 response at the first observation after challenge, and treatment with the safeguard dose would give some response, the observed transient biological response (barely perceptible erythema in 70 % of the animals at 48 hours) was considered not to represent an immune reaction.

In this study, 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues was not a skin sensitiser.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a dermal sensitisation study (Török-Batho, 2010) with 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues (≥98 %) in sesame oil, young adult Hartley guinea pigs (test group: 10 males, control group: 5 males) were tested according to the method of Magnusson and Kligman. For intradermal and topical induction treatment 5 % and 100 % were used, respectively, representing the highest concentrations causing mild-to-moderate skin irritation. Challenge with the test item resulted in a mean score of 0.70 (7/10) and 0.20 (2/10) at the 48 and 72 hour observations (24 and 48 hours after patch removal), respectively. The net response value was 70 %, as barely perceptible erythema at the first observation. However, the net response value at the second observation was only 20 %. No signs of skin reaction were noted following treatment with the safeguard concentration (corresponding to 50 % of the challenge concentration). Since for an immune response it would be expected that under the conditions of this study many animals treated with the challenge dose would have a reaction persisting to the second observation, there would be at least some animals with a grade 2 or 3 response at the first observation after challenge, and treatment with the safeguard dose would give some response, the observed transient biological response (barely perceptible erythema in 70 % of the animals at 48 hours) was considered not to represent an immune reaction.

In this study, 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues was not a skin sensitiser.


Migrated from Short description of key information:
The reliable key study shows no indication for skin sensitisation by exposure to 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues.

Justification for selection of skin sensitisation endpoint:
Guideline study according to GLP

Justification for classification or non-classification

Based on the key study results, the tested substance 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues is not subject to classification and labelling for sensitisation according to Directive 67/548/EEC and Regulation 1272/2008/EC.