Heptan-1-ol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 May 2011 - 22 July 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guidelines; adequate coherence between data, comments and conclusions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

two animals were evaluated for skin reactions at 44.25h after removal of dressing instead of 48h

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

idem above

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A magnusson and Kligman was performed in order to verify the result obtained in the LLNA study as it is a maximization test..

Test material

Test material information

Constituent 1

Reference substance name:

Heptan-1-ol

EC Number:

203-897-9

EC Name:

Heptan-1-ol

Cas Number:

111-70-6

Molecular formula:

C7H16O

IUPAC Name:

heptan-1-ol

Details on test material:

- Name of test material (as cited in study report): N-HEPTANOL
- Physical state: colorless liquid
- Analytical purity: 99.73%
- Lot/batch No.: 1103016
- Expiration date of the lot/batch: 09 December 2011
- Storage conditions of test material: at room temperature, well-ventilated place.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Breeder: Charles River Laboratories France, L’Arbresle, France
- Age at study initiation: at the beginning of the treatment period, the animals of the main test were 1-2 months old
- Weight at study initiation: 307 g ± 10 g for the males and 304 g ± 10 g for the females
- Housing: individually housed in polycarbonate cages with stainless steel lid
- Diet (e.g. ad libitum): free access to 106 pelleted diet
- Water (e.g. ad libitum): tap water (filtered with a 0.22 µm filter)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00).

IN-LIFE DATES: From: 07 June 2011 To: 22 July 2011

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: corn oil (intradermal); ethanol/drinking water (topical induction); acetone (topical challenge)

Induction 2

Concentration / amount:

1% intradermal, 100% topical induction, 10% topical challenge

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: corn oil (intradermal); ethanol/drinking water (topical induction); acetone (topical challenge)

Challenge 2

Concentration / amount:

1% intradermal, 100% topical induction, 10% topical challenge

No. of animals per dose:

in treated groups of main test:
10 males and 10 females

Details on study design:

RANGE FINDING TESTS:
Performed to determine maximum concentrations tested in the main test

MAIN STUDY
See executive summary

Challenge controls:

left flank: vehicle only

Positive control substance(s):

not required

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% (challenge)

No. with + reactions:

1

Total no. in group:

20

Clinical observations:

discrete erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% (challenge). No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: discrete erythema.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10% (challenge)

No. with + reactions:

4

Total no. in group:

20

Clinical observations:

discrete erythema; dryness of skin

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10% (challenge). No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: discrete erythema; dryness of skin.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item did not induce delayed contact hypersensitivity in guinea pigs.

Executive summary:

The objective of this study was to evaluate the potential of the test item, n-HEPTANOL (batch No. 1103016), to induce delayed contact hypersensitivity in guinea pigs.

This study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

A preliminary test was first performed in order to determine the test item concentrations to be used in the main test.

In the main test, one group of 10 males and 10 females received the test item:

.          on day 1 by intradermal injections in the interscapular region at the concentration of 1%,

.          on day 8 by topical application to the clipped interscapular region at 100%,

.          on day 22 by topical application to the posterior right flank at 10%. The posterior left flank of the animals received the vehicle.

Another control group of five males and five females received the vehicles:

.             corn oil on day 1 in the interscapular region,

.            drinking water treated by reverse osmosis on day 8 in the interscapular region,

.            acetone on day 22 to the posterior left flank. The posterior right flank of animals received the test item at 10%.

 

On day 1, three pairs of intradermal injections were performed in the interscapular region of animals:

.          Freund's complete adjuvant (FCA) diluted to 50% (v/v) with 0.9% NaCl,

.          test item in vehicle or vehicle alone,

.          test item in FCA/0.9% NaCl (50/50, w/w) or vehicle at 50% (w/v) in FCA/0.9% NaCl (50/50, v/v).

 

On day 8, a filter paper (approximately 8 cm²) was fully-loaded with the dosage forms and then applied to the clipped interscapular region, over the intradermal injection sites. The filter paper was held in place by means of an occlusive dressing for 48 hours. The presence of local irritation was checked (but not scored).

The induction phase was followed by a 14-day rest period.

 

On day 22, a Finn Chamber filter paper was fully-loaded with the dosage forms. The chamber was held in contact with the skin by an occlusive dressing for 24 hours. Cutaneous reactions were evaluated before treatment and 24 and 48 hours after removal of the dressing.

 

Each animal was observed at least once a day for mortality and clinical signs during the treatment and observation periods. Body weight was recorded on day 1 and at the end of each observation period.

On completion of the observation period, the animals were sacrificed then discarded without macroscopic post-mortem examination. No skin samples were preserved.

 

Results

After the challenge application, in the control group, at the 24-hour reading, a discrete erythema was observed at right flank treated with test item of 1/10 animals. At the 48-hour reading, a discrete erythema was observed at left flank treated with vehicle of 1/10 animals.

 

In the test item-treated group, at the 24-hour reading, a discrete erythema was noted at right flank treated with test item of 1/20 animals.

At the 48-hour reading, a discrete erythema was observed at left flank treated with vehicle of 1/20 animals and at right flank treated with test item of 4/20 animals. In addition, dryness of the skin was noted at right flank of 1/20 animals.

As the cutaneous reactions were similar at right flank treated with test item and at left flank treated with vehicle, they were considered not to be attributed to delayed contact hypersensitivity.

Conclusion

The test item did not induce delayed contact hypersensitivity in guinea pigs. 

Therefore, the test item should not be considered as sensitizing.