(Z)-N-9-octadecenylpropane-1,3-diamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-11-16 to 2007-04-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-N-9-octadecenylpropane-1,3-diamine

EC Number:

230-528-9

EC Name:

(Z)-N-9-octadecenylpropane-1,3-diamine

Cas Number:

7173-62-8

Molecular formula:

C21H44N2

IUPAC Name:

N-[(9Z)-octadec-9-en-1-yl]propane-1,3-diamine

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): N-Oleyl-1,3-diaminopropane
- Physical state: liquid
- Analytical purity: N-Alkyl-1,3-diaminopropanes: 92.3%
N-Alkyl-amines: 7.7%
C-Chain-distribution (R = alkyl):
R = C16: 7%; C18: 91%; C20: 2%
- Lot/batch No.: S000902
- Production date of the test item: August 13, 2007
- Expiration date of the lot/batch: September 30, 2010
- Storage condition of test material: at room temperature
- Product (name): Duomeen OV
- Colour: Max 7 Gardner
- Melting Point: 9 - 20°C
- pH: basic

Test animals

Species:

rabbit

Strain:

other: New Zealand White HsdIf:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: 2.13 to 2.7 kg
- Housing: in ABS - plastic rabbit cages, floor 4200cm²
- Diet (e.g. ad libitum): free access to Altromin 2123 maintenance diets for rabbits, rich in crude fibre
- Water (e.g. ad libitum): free access to tap water (microbiologically controlled periodically)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +- 3°C
- Humidity (%): 55 +- 10%
- Air changes (per hr): at least 10x/h
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

other: Initial test: semiocclusive, additional test: held in place manually

Preparation of test site:

other: clipping

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin areas of the test animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): for the initial test and the additional test 0.5 mL

Duration of treatment / exposure:

initial test: 4h

additional test: 3min

Observation period:

1, 24, 48, 72h after patch removal

Number of animals:

2 (1 animal/ initial test, 1 animal/ additional test)

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: small area of approximately 6cm²

REMOVAL OF TEST SUBSTANCE - INITIAL TEST
- Washing : rinsed by using tap water
- Time after start of exposure: at the end of the exposure period (4 h)

REMOVAL OF TEST SUBSTANCE - ADDITIONAL TEST
- Washing : no
- Time after start of exposure: 3 min after start of exposure the patch was removed without washing

SCORING SYSTEM:
according to guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: PSI, initial test

Basis:

animal #1

Time point:

other: average over 24/48/72h

Score:

8

Max. score:

4

Reversibility:

not reversible

Remarks:

animal was euthanized after 72h due to animal welfare reasons

Remarks on result:

other: Necrosis was observed at all times

Results 2

Irritation parameter:

other: PSI, additional test

Basis:

animal #2

Time point:

other: average over 24/48/72h

Score:

8

Max. score:

4

Reversibility:

not reversible

Remarks:

animal was euthanized after 72h due to animal welfare reasons

Remarks on result:

other: Necrosis was observed after 24h and 48h.

Results 3

Irritation parameter:

other: result after 3 min, additional test, PSI

Basis:

animal #2

Time point:

other: 3 min

Score:

1

Max. score:

1

Reversibility:

not reversible

Remarks:

within 72h

Remarks on result:

other: Erythema formation was observed immediatly

Irritant / corrosive response data:

Dermal irritation was scored and recorded according to the grades stated in the guidelines. The test item showed severly irritant effects on the intact skin of both rabbits after a contact time of 4h or 3min.

Other effects:

Necrosis was observed, refer to Table 1.
Animal 1 showed weight loss during the observation period.

Any other information on results incl. tables

Table 1: Dermal irritation of animal 1 and 2

	3 min		1 h		24 h		48 h		72 h
Animal number	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1 initial test	-	-	3	4	4*	4	4*	4	4*	4
2 additional test	1	0	0	2	4*	4	4*	4	4	4

* : necrosis covering half the patch area

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the criteria of the Commission Directive 2001/59/EC, the test item N-Oleyl-1,3-diaminopropane has to be classified and has obligatory labelling requirement for skin corrosion.

Executive summary:

Acute dermal irritation/corrosion of N-Oleyl-1,3-diaminopropane (liquid) was investigated. 0.5mL of the test substance were applied via a semiocclusive gauze patch to intact clipped skin of one female New Zealand White rabbit and held in place for 4h. At the end of the exposure period, residual test item was rinsed with tap water. In an additional test 0.5mL were applied via a gauze patch to intact clipped skin of another female New Zealand White rabbit and held in place manually for only 3min without subsequent rinsing. Animals were examined for signs of erythema and oedema at 1, 24, 48, 72h after patch removal.

Calculation of Primary Irritation Scores (PIS) as an average value over 24h, 48h and 72h was calculated for each animal. This yielded values of 8 for both animals. Necrosis was observed after 24h in both animals. Irritant effects were not reversible and occurred as early as 3min after exposure (additional test) and persisted. 1 Animal displayed weight loss during the observation period. The symptoms after a contact period of both 4h or 3min required euthanisation of the animals due to animal welfare reasons shortly after the end of the 72h observation period.

Considering the reported data of this irritation study it can be stated that the test item N-Oleyl-1,3-diaminopropane showed severely irritant effects. According to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 2001/59/EC) the test item N-Oleyl-1,3-diaminopropane has to be classified as corrosive and has obligatory labelling requirement for skin irritation.

The test on acute dermal irritation/corrosion was performed under GLP and similar to guideline OECD Guideline 404, EU Method B.4 and EPA OPPTS 870.2500 without deviations.