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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:
weight of evidence
Study period:
From August 23 to September 29, 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study conducted according to OECD test Guideline No. 406 without any deviation. The study was fully reliable (Klimisch score = 1), however the reliability score was lowered to 2 which is the maximum score for read-across. The supporting substance is considered adequate for read-across purpose (see IUCLID section 13 for additional justification).
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test was conducted before establishment of LLNA method

Test material

Constituent 1
Reference substance name:
2-pentylcyclopentan-1-ol
EC Number:
283-187-3
EC Name:
2-pentylcyclopentan-1-ol
Cas Number:
84560-00-9
IUPAC Name:
2-pentylcyclopentanol
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): ST 22 C 95
- Physical state: liquid
- Lot/batch No.: MH 390
- Expiration date of the lot/batch: no data
- Storage condition of test material: room temperature in the dark
- Other: reception date: 1995-08-18

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Darley Oaks, Burton-on-Trent, Staffordshire, England.
- Age at study initiation: young
- Weight at study initiation: 250-300 g
- Housing: in groups of up to 5 in stainless steel grid bottomed cages.
- Diet (e.g. ad libitum): pelleted diet ad libitum (SQC FD1 guinea pig diet with added vitamin C produced by Special Diets Services, Witham, Essex).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days for the animals used for the preliminary study and 18 days for those selected for the main tests.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 40-69 %
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: light liquid paraffin for intradermal induction
Concentration / amount:
- Intradermal induction: 5%
-Topical induction: 100 %
- Challenge: 100 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: light liquid paraffin for intradermal induction
Concentration / amount:
- Intradermal induction: 5%
-Topical induction: 100 %
- Challenge: 100 %
No. of animals per dose:
5 preliminary test animals, 20 test animals, 10 control animals
Details on study design:
RANGE FINDING TESTS:
- Intradermal injections: 0.1 mL aliquot of 50%, 25%, 10%, 5%, 1% and 0.5% v/v concentrations in light liquid paraffin. 1 guinea-pig pretreated 7 d before with 4 intradermal injections of 1:1 FCA/water. The highest concentration which produced an acceptable localised response at each injection site was 5%.
- Topical induction and challenge: 100%, 50%, 25% and 12.5% v/v in diethylphtalate. 4 guinea-pigs pretreated with FCA/water as described above. Undiluted test article was found to be non-irritant when applied topically and was therefore selected for the topical induction phase and the challenge phase of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2, intradermal injections and topical application
- Exposure period: 48h for topical application
- Test groups:
INTRADERMAL: 3 pairs of intradermal injection (0.1 mL) on Day 0 as follows:
- 1/ 50% v/v FCA/distilled water
- 2/ test substance 5% in light liquid paraffin
- 3/ test substance 5% in 50:50 distilled water/FCA
Six days after the intradermal induction, as the undiluted test material was non-irritant, the test area of all animal was treated topically with 10 % sodium lauryl sulphate in light liquid paraffin in order to produce irritation.
TOPICAL: 7 days after intradermal injections, the test substance (100%) was applied (patches of Whatman No. 3 filter paper, 4cm x 2cm) and covered with a strip of "Blenderm" surgical tape secured in place and wrapped with "Elastoplast" elastic adhesive bandage (occlusive tape).
- Control group: similarly treated with the exception that the diethylphtalate was topically applied instead of the test substance
- Site: clipped dorsal area between the shoulders

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 d after the topical induction application, i.e. 21 d after study initiation
- Exposure period: 24 hours
- Test and control groups: 100% on the anterior aspect of the left flank. Similarly treated than topical induction (patches 2cm x 2 cm). Right flanks were treated with vehicle alone (diethylphtalate):
- Site: flanks
- Concentrations: 100%
- Evaluation (hr after challenge): approximately 24 and 48 hours after patch removal.
Challenge controls:
Hexyl cinnamic aldehyde was used as a positive control as this is known to be a sensitizer. The material was administered as a 25 % concentration in light liquid paraffin for the intradermal injections and a 50 % concentration in ethanol for the topical induction (after 10% SLS application). Challenge was conducted at concentrations of 50% in acetone. This positive control study took place during the period from 1995-02-22 to 1995-03-18
Positive control substance(s):
yes
Remarks:
Hexyl cinnamic aldehyde

Results and discussion

Positive control results:
8 out 10 in the test group gave positive response to 50 % Hexyl cinnamic aldehyde resulting in a response incidence of 80 %. None of the animals in the test group exhibited positive response to acetone alone. None of the animals in the control group responded positively to 50% hexyl cinnamic aldehyde or acetone alone. These results confirm that hexyl cinnamic aldehyde is a sensitizer under the conditions of this study and the test system is therefore considered to be validated.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50%
No. with + reactions:
8
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
1 animal was killed in extremis on the day of patch removal following topical induction and was found to have a prolapsed uterus following a post-mortem examination
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: 1 animal was killed in extremis on the day of patch removal following topical induction and was found to have a prolapsed uterus following a post-mortem examination.
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 19.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0 %
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
one control animal was found dead in its cage prior to the challenge application. No abnormalities were detected following a post-mortem examination
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 %. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: one control animal was found dead in its cage prior to the challenge application. No abnormalities were detected following a post-mortem examination.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test material is not classified as a skin sensitizer according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC
Executive summary:

In a dermal sensitization study performed according to the OECD test guideline no. 406 and in compliance with GLP, the test material was tested in female Hartley guinea-pigs using the Guinea-Pig Maximisation Test method (20 treated animals + 10 controls).

The preliminary study determined the concentration to be used for the induction and challenge phases of the main study.

 

The test material, diluted in light liquid paraffin at 5% (v/v), was administered by injection for intradermal induction. As the substance was not a skin irritant, 24 hours prior to the topical application, the site was pre-treated with 10% w/w sodium lauryl sulphate in light liquid paraffin. Topical induction was performed with the test material as supplied, 7 days after intradermal injections. For the challenge, 21 days after study initiation, the test material was tested undiluted.

 

One test animal was killed in extremis on the day of patch removal following topical induction and was found to have a prolapsed uterus following a post-mortem examination.

Following challenge, none of the remaining 19 test animals responded positively at the 24 or 48 hour observations, resulting in a response incidence of 0 %. Similarly, none of the 19 animals responded positively to challenge with the vehicle.

 

One control animal was found dead in its cage prior to the challenge application. No abnormalities were detected following a post-mortem examination.

None of the remaining 9 control animals responded positively to challenge with either undiluted test article or the vehicle (diethylphtalate), at any of the observations, resulting in a response incidence of 0 %.

 

The historical positive control, hexyl cinnamic aldehyde, produced evidence of skin sensitization in 8 of 10 animals at 50 %, resulting in a response incidence of 80 %. These results confirmed that hexyl cinnamic aldehyde is a sensitizer under the conditions of this study and the test system was therefore considered to be validated.

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for sensitisation endpoint.