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Administrative data

Description of key information

There are two studies available on Amines, N-C16-18-alkyl (evennumbered) propane-1,3-diamine, resulting to severe dermal irritation close to corrosive response.

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 2007-12-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
other: New Zealand White HsdIf:NZW
Details on test animals 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
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
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.
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.
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.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible
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.

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

 

    24h

    48h

    72h

 Animal number

 Erythema

 Oedema  Erythema  Oedema  Erythema  Oedema
 1   2* 3* 3* 2
 2  2 2* 2* 
 3  2 2*  2* 

* : eschar formation

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dermal irritation:

Two studies are available that evaluated the potential for skin irritation and corrosion of N-(hydrogenated tallow alkyl) trimethylenediamine (Amines, N-C16-18-alkyl (evennumbered) propane-1,3-diamine, CAS 133779-11-0, also referred to as HT-diamine). Both studies were performed according to OECD 404 and under GLP.

In the first study (BSL, 2008) 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.

Average Primary Irritation Scores (PIS) for 24, 48 and 72 hrs were 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), fully reversible by day 9 or 14.

 

In the second study (SPL, 1988) three animals were exposed to 0.5 g test substance for 4 hours and after this period the dressing was removed and the skin was decontaminated by gentle swabbing with cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled water alone.

Well-defined erythema and slight oedema were noted at all treated skin sites one hour after removal of the patches. Well-defined erythema with a light brown-discolouration of the skin, and very slight or slight oedema, was noted at all treated skin sites at the 24, 48 and 72-hour observations. Loss of suppleness of the skin was also apparent at two of the treated skin sites during this period. Adverse dermal reactions at the end of the observation period on day seven were dry straw-coloured flaking skin (possible hyperkeratinisation) at two treated skin sites and glossy skin (keratolysis) at the remaining treated skin site. No full recovery was observed at the end of the observation period, however, the test material produced no evidence of visible necrosis following an exposure period of 4 hours.

 

All available data on the category of the diamines, indicate that all other besides this hydrogenated tallow-diamine are corrosive to skin, and classified as corrosive Cat. 1B (See table):

C12-14, Coco, Oleyl: As can be seen, C12-14, Coco and Oleyl diamines are all corrosive following 3 minute exposures, with in depth skin destruction only becoming visible at 24 hr readings, resulting to Cat.1B classification.

Tallow: For the Tallow, the 3 minute exposures do not lead to corrosion, but as the 1 hr exposure leads to corrosion, it still classifies as Cat. 1B. The Tallow seems to be a little less corrosive compared to the shorter chains and Oleyl. Unfortunately this substance has not been included in the BSL testing program at the time, so direct comparison of results is a bit less clear. It should be remarked that contrary to the recent BSL studies, the skin was decontaminated immediately after exposure. However, the same was done in the CESIO studies at SPL for Coco where the 3 minute exposures still resulted to corrosion.

HT: Contrary to the other diamines the HT is not corrosive, but severely irritating. However, in view of the overall information on the category of alkyl-diamines, it is best to take care to limit possible dermal exposures.

 

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)

Oleyl

Cat. 1B

BSL 073802E, 2008

3 min (liquid/paste): Corrosive after 24 hrs

 

Cat. 1B

BSL 073802A, 2008

3 min (liquid): Corrosive after 24 hrs

 

Cat. 1B

CIT 19300 TAL, 2000

3 min (liquid): Corrosive (Crusts tissue from 24 hrs)

Tallow

Cat. 1B

SPL 116/28, 1987

(Diamine BG)

3 min: Irritant (skin decontaminated)

1 hr: Corrosive

 

Cat. 1B

SPL 1594-191/1-18, 1989

3 min: Irritant (skin decontaminated)

1 hr: Corrosive

 

n.a.

SPL, Cesio, 1991

3 min: Irritant (skin decontaminated)

HT

Cat. 2

BSL 073802D, 2008

4hr: Strongly irritating. Eschar formation was observed after 24h (animal 1) or after 48h (animal 2 and 3), fully reversible by day 9 or 14.

 

Cat. 2

SPL 116/37, 1988

4hr: Irritating: at end of observation: dry straw-coloured flaking skin (possible hyperkeratinisation) at two treated skin sites and glossy skin (keratolysis) at the remaining treated skin site.

 

 

Eye irritation:

Due to the severe irritant, close to corrosive response (even eschar formation was observed in all treated animals) observed in de dermal irritation/corrosion studies with this substance it is not ethical to carry out this animal study. In view of the severe reactions to skin, serious eye damage is to be expected.

 

Respiratory irritation:

N-(hydrogenated tallow alkyl) trimethylenediamine is a solid (pellets) with mp of 43°C, with no inhalable particles (0.11% (m/m) with particle size < 100 μm) and a vapour pressure less than 0.0015 Pa at 20°C (value based on read-across from shorter chain C12-14-diamine). 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.

Justification for classification or non-classification

The available studies indicate that N-(hydrogenated tallow alkyl) trimethylenediamine should regarded as a severe irritant (even eschar formation was observed in all treated animals), but not corrosive.

Consequently, GHS classification Cat.2 skin irritation is appropriate, with hazard statement H315: Causes skin irritation.

 

In view of the severe irritant properties, it is prudent to classify the substance for serious eye damage Cat. 1, with hazard statement H318: Causes serious eye damage.

 

STOT-SE Cat.3 for respiratory irritation is not required. Exposure to via the inhalation route will be unlikely to occur. Consequently, despite the irritant nature of the substance, respiratory irritation is not expected.