1-[(2-butyloctyl)oxy]-3-(3,4-dihydroisoquinolinium-2-yl)propan-2-yl sulfate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2006-03-29 to 2006-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2004/73/EC

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Sokalan PG B62;

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Age at day 0: About 7 months
Sex: 1 male and 2 females
Supplier: Centre Lago S. A., 01540 Vonnas, France
Arrival in the testing facility: Acclimatization for at least 5 days before application
Body weight range at day 0: 3.71 kg – 4.12 kg
Room temperature/relative humidity: The animals were housed (single housing) in fully air-conditioned rooms.
Central air-conditioning guaranteed a range of 20 – 24°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Day / night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Stainless steel wire mesh cages with grating, floor area: 3000 cm²
Feeding: Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
Drinking: tap water ad libitum.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

Concentration: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 (2 females, one male)

Details on study design:

Clipping of the fur: At least 24 hours before the beginning of the study, fur was clipped from the dorsolateral part of the trunk of the animal(s) (flank)
Body weight determination: Body weights were determined just before application of the test substance and after the last reading.
Route of application: The test substance was applied in a single dose to the intact untreated skin. The test patch was secured in position with a semiocclusive dressing. The test substance was removed at the end of the exposure period with Lutrol® and Lutrol® / water (1 : 1).
Application volume: The test patch (2.5 cm x 2.5 cm) was covered with an amount of minimally moistened solid preparation corresponding to a dos of 0.5 g of undiluted test substance.
Application site: Flank
Negative control: Untreated skin sites of the same animal.
Readings: Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch.
Mortality: A check for any dead or moribund animal was made twice each workday (at the beginning and end of work) and once daily at weekends and on public holidays.
Terminal procedures: All animals were killed with a lethal injection of Narcoren® into the ear vein and discarded. Necropsies were not performed.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-72h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-72h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-72h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritant / corrosive response data:

Slight or moderate erythema (grade 1 or 2) were observed in all animals immediately after removal of the patch, and at 1 and 24 h. Slight erythema persisted in two animals at the 48 h reading. No edema or other cutaneous reactions were observed at any time during the study. One animal had recovered fully by the 48 h grading. The two other animals had recovered by 72 h.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Skin irritation/corrosion of 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate was investigated in an in vivo test in rabbits. Mean scores over 24, 48 and 72 hours for each animal were 1.0, 0.3 and 0.7 for erythema and 0.0 for edema. Thus, the test substance is not irritating to the skin.

Executive summary:

In a GLP conform dermal irritation/corrosion test in White New Zealand rabbits an amount of 0.5 g of the test substance was applied for 4 hours to the intact skin of three rabbits, using a patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch.

Slight or moderate erythema were observed in all animals during the observation period. The cutaneous reactions were reversible in all animals within 72 hours after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 1.0, 0.3 and 0.7 for erythema and 0.0 for edema.

Considering the described cutaneous reactions as well as the average score for irritation, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate does not show a skin irritation potential under the test conditions chosen.