2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]henicosan-21-one hydrochloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-06-04 till 2008-06-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline-conform study under GLP without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]henicosan-21-one hydrochloride

EC Number:

277-620-5

EC Name:

2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]henicosan-21-one hydrochloride

Cas Number:

73833-37-1

Molecular formula:

C22H40N2O2.xClH

IUPAC Name:

2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]henicosan-21-one hydrochloride

Details on test material:

- Name of test material (as cited in study report): 2,2,4,4-tetramethyl-7-oxa-3,20-diazadispiro[5.1.11.2]henicosan-21-one hydrochloride
- Physical state: solid, white
- Analytical purity: => 99%
- Lot/batch No.: DEF2036584
- Expiration date of the lot/batch: 2018-05-08
- Stability under test conditions: stable
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV
- Age at study initiation: 14 weeks (male), 15-16 weeks (females)
- Weight at study initiation: 2600 g (male), 2503 g and 2819 g (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 2008-06-04 to 2008-06-08


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: closely clipped

Vehicle:

other: moistened with purified water

Controls:

other: control area on same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per animal

VEHICLE
- Purity: purified water

Duration of treatment / exposure:

4 hrs

Observation period:

1, 24, 48 and 72 hours after exposure

Number of animals:

3 (one male, two females)

Details on study design:

TEST SITE
- Area of exposure: left flank (10 cm x 10 cm)
- % coverage: ca. 2.5 cm x 2.5 cm
- Type of wrap if used: surgical gauze patch


REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water (after dressing removal)
- Time after start of exposure: 4 hrs


SCORING SYSTEM: numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 hrs

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hrs

Score:

0

Max. score:

0

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Edema
	Max. score: 0	Max. score: 0
60 min	0/0/0	0/1/1
24 h	0/0/0	0/0/0
48 h	0/0/0	0/0/0
72 h	0/0/0	0/0/0
Average 24h, 48h, 72h	0/0/0	0/0/0
Reversibility*)	-	-
Average time (unit) for reversion	-	-

 

*) Reversibility: c. = completely reversible; = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the referred classification criteria of the Commission Directive 2001/59/EC of August 2001, Hostavin N 20 - Hydrochlorid is considered to be “not irritating” to rabbit skin.

Executive summary:

The irritation potential to skin was investigated acc. to OECD guideline 404 in rabbits.

The test item was applied by topical semi-occlusive application to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours.

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. No abnormal findings were observed on the treated skin of any animal. No staining produced by the test item of the treated skin was observed. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin. The male did not gain weight from the day of treatment to the last day of observation. The body weights of all rabbits were considered to be within the normal range of variability.