Amines, N-C16-18-alkyltrimethylenedi-

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 2007-12-21

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:

Amines, N-C16-18-alkyl (evennumbered) propane-1,3-diamine

EC Number:

696-364-9

Cas Number:

133779-11-0

Molecular formula:

Not applicable

IUPAC Name:

Amines, N-C16-18-alkyl (evennumbered) propane-1,3-diamine

Test material form:

solid: pellets

Details on test material:

- Substance type: Diamine
- Name of test material (as cited in study report): N-(Hydrogenated tallow)-1,3-diaminopropane
- CAS: 68603-64-5- Physical state: pellets
- Colour: light yellow
- Composition of test material, percentage of components:

Total primary amines: 9.6 %
Total Diamines: 90.4 %
Iodine number: 3 g I/100g (0-10)
Water: 0.6 % (0-1)

C12 N Primary amine: 0.1 %
C14 N Primary amine: 0.2 %
C16 N Primary amine: 3.0 %
C18 N Primary amine: 6.3 %
C12 Diamine: 0.3 %
C14 Diamine: 1.5 %
C16 Diamine: 28.3 %
C18 Diamine: 60.3 %
Acrylnitrile: <4 ppm
Fatty acids: <1 %
Fatty alkyl nitriles: <1 %

- Purity test date: 2007-10-15
- Lot/batch No.: S000905
- Expiration date of the lot/batch: 2010-09-30
- Storage condition of test material: at room temperature

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: 2.2 to 3.0kg
- 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:

semiocclusive

Preparation of test site:

other: clipping

Vehicle:

other: aqua ad inject.

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): 0.5g (ground finely by using a mortar before)

VEHICLE
- Amount(s) applied (volume or weight with unit): only for moistening of test substance
- Lot/batch no. (if required): 15608D (Delta Select)
- Purity: no data

Duration of treatment / exposure:

4h

Observation period:

1, 24, 48, 72h after patch removal; animals were observed daily for reversibility of irritating effects up to day 13

Number of animals:

3

Details on study design:

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

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed by using tap water or aqua ad inject.
- Time after start of exposure: at the end of the exposure period

SCORING SYSTEM:
according to guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: Eschar formation was observed at all times.

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 13 days

Remarks on result:

other: Eschar formation was observed after 48h and 72h.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 13 days

Remarks on result:

other: Eschar formation was observed after 48h and 72h.

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible

Irritant / corrosive response data:

Dermal irritation was scored and recorded according to the grades stated in the guidelines.

Other effects:

Eschar formation was observed, refer to Table 1.
Weight gain during the contact and observation period was normal for all animals.

Any other information on results incl. tables

Table 1: Dermal irritation of animal 1, 2 and 3

	24h		48h		72h
Animal number	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1	2*	2	3*	2	3*	2
2	2	3	2*	3	2*	3
3	2	2	2*	3	2*	3

* : eschar formation

Applicant's summary and conclusion

Interpretation of results:

irritating

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-(Hydrogenated tallow)-1,3-diaminopropane has to be classified and has obligatory labelling requirement for skin irritation.

Executive summary:

Acute dermal irritation/corrosion of N-(hydrogenated tallow)-1,3-diaminopropane was investigated. The test substance was ground finely by using a mortar before application of 0.5g. To ensure good contact, it was moistened with aqua ad inject. Three female New Zealand White Rabbits were exposed 4h after removing fur from the dorsal area of the trunk. At the end of the exposure period, residual test substance was rinsed by using tap water or aqua ad inject. Animals were examined for signs of erythema and oedema at 1, 24, 48, 72h after patch removal. Then, animals were observed daily for reversibility of irritating effects up to day 13.

Calculation of Primary Irritation Scores (PIS) as an average value over 24h, 48h and 72h was calculated for each animal. This yielded values of 4.7 (animal 1 and 3) and 5.0 (animal 2), respectively. Eschar formation was observed after 24h (animal 1) or after 48h (animal 2 and 3), respectively. Irritant effects were fully reversible within 9 or 14 days. Weight gain during the contact and observation period was normal for all animals.

Considering the reported data of this irritation study it can be stated that the test item N-(Hydrogenated tallow)-1,3-diaminopropane showed well-defined to moderate irrant effects, which were fully reversible 9 days after patch removal in animal 1 and 13 days after patch removal in animals 2 and 3.

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-(Hydrogenated tallow)-1,3-diaminopropane has to be classified 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.