Amines, N-C12-14-alkyltrimethylenedi-

Endpoint summary

Description of key information

Corrosive properties are observed following exposures of 3 minutes and longer, with the skin destruction becoming visible after some delay.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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)

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: 2.1 to 2.2kg
- 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

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 0.5mL

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 (4h)

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

SCORING SYSTEM:
according to guideline

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

other: PSI, initial test

Basis:

animal #1

Time point:

24/48/72 h

Score:

8

Max. score:

12

Reversibility:

not reversible

Remarks:

animal was euthanized after 72h due to animal welfare reasons

Remarks on result:

other: Necrosis was observed at all times

Irritation parameter:

other: PSI, additional test

Basis:

animal #2

Time point:

24/48/72 h

Score:

7.7

Max. score:

12

Reversibility:

not reversible

Remarks:

animal was euthanized after 72h due to animal welfare reasons

Remarks on result:

other: Necrosis was observed at all times

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.
No weight loss was observed during the observation period.

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	-	-	4*	4	4*	4	4*	4	4*	4
2 additional test	1	0	1	2	4*	3	4*	4	4*	4

* : necrosis covering the entire area

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

According to the criteria of the Commission Directive 2001/59/EC, the test item N-C12,14 alkyl-1,3-diaminopropane has to be classified and has obligatory labelling requirement for skin irritation.

Executive summary:

Acute dermal irritation/corrosion of N-C12,14 alkyl-1,3-diaminopropane (liquid/paste) was investigated. 0.5 mL 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 4 h. 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 the animal in the inital test and 7.7 for the animal in the additional test. Necrosis was observed after 4h in animal 1 and after 24h in animal 2. Irritant effects were not reversible and occurred as early as 3min after exposure (additional test) and persisted. 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-C12,14 alkyl-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-C12,14 alkyl-1,3-diaminopropane has to be classified as corrosive category 1B, with hazard phrase H 314: Causes severe skin burns and eye damage.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Dermal irritation:

There one studies available that evaluated dermal irritation /corrosive properties of N-C12,14 alkyl-1,3-diaminopropane (CAS 90640-43-0, also referred to as C12-14-diamine).

In this study (BSL, 0 073802C, 2008), C12-14-diamine was investigated in an in vivo OECD 404 guideline study under GLP. The test substance was investigated by administration of 0.5mL unchanged test substance. In the initial test, one female New Zealand White (NZW) rabbit was exposed 4h after removing fur from the dorsal area of the trunk, and another animal was exposed for 3 minutes. At the end of the 4 hour exposure period, residual test substance was rinsed by using tap water. No rinsing was performed after the 3 minute exposure.

Necrosis covering the entire patch was observed in both animals. Necrosis was already observed 1 hour after patch removal following 4 hours exposure, but following 3 minutes exposure, necrosis was visible the next day, but not yet at one hour after exposure.

The results following the 3 minute exposure can possibly be considered to represent a too severe evaluation. Without removal of the (sticky) test substance, there is in principle no difference expected between the results after 4 hour and 3-minute exposures. Indeed, the comparable observation times at 24 hours after exposure and later, show the same effects for both application schemes.

 

However, when comparing with data from Coco-diamine with an average chain length comparable to the C12-14-daimine, the data show a consistent pattern for corrosive properties for this substance (See table):

 

Chain	Class	Study	Result
C12-14	Cat. 1B	BSL 073802C, 2008	3 min: Corrosive after 24 hrs
Coco	Cat. 1B	BSL 073802B, 2008	3 min: Corrosive after 24 hrs
	Cat. 1B	SPL 1594-191/1-18, 1989	3 min: Corrosive (skin decontaminated) effects indicative for corrosion were visible from 24 hours; 1/6 animals showed scar after 14 days
	Cat. 1B	SPL, Cesio, 1991	3 min: Corrosive (skin decontaminated) Scar tissue in 3/6 animals after 14 days, effects indicative for corrosion were visible from 24 hours
	n.a.	F&D Res.Lab, SD-1684, 1981	24 hrs: Corrosive (Eschar formation (dead skin) visible at 24 and 72 hrs. No later observations)

 

Eye irritation:

Due to corrosive properties in de dermal irritation/corrosion studies with this substance testing in eyes would not be required.

Justification for classification or non-classification

Available data indicate corrosive properties following exposures of 3 minutes and longer. Following exposure of 3 minutes, the skin destruction is observed at examination the next day, but not yet at the observation 1 hour after the exposure.Consequently, GHS classification Corrosive Category 1B is appropriate, with hazard statement H314: Causes severe skin burns and eye damage.

 

Due to corrosive properties demonstrated in the dermal irritation/corrosion study with this substance, testing in eyes is not justified. Under GHS with the hazard phrase ‘H314 Causes severe skin burns and eye damage’ additional classification for eyes is not necessary.

 

There is no information is available following exposure via inhalation. However, with a vapour pressure of 0.0015 Pa at 20°C, potential for inhalation of vapours is limited. Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Consequently, despite the irritant nature of the substance, respiratory irritation is not expected, and classification STOT-SE Cat.3 for respiratory irritation is not required.