N-C16-18-alkyl-(evennumbered) C18 unsaturated) propane-1,3-diamine

Endpoint summary

Description of key information

Corrosive properties are observed following exposures of 1 hour 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:

23 september 1987 - 7 october 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD 404; Substance is old tradeName of AkzoNobel product; No CoA available.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Limited, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.45 up to 2.78 kg
- Housing: individually in suspended metal cages with metal grid bases
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: five days at least


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 14-21 °C
- Humidity (%): 50-65%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

3 minutes then 1 hour

Observation period:

Cutaneous reactions were evaluated approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
If adverse skin reactions were noted at the 72-hour reading, additional observations were made on days 7 and 14 after treatment.

Number of animals:

three animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm X 2.5 cm for each test site. Two test sites per rabbit.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was decontaminated by gentle swabbing with cotton wool soaked in 3% (v/v) aqueous acetic acid followed by distilled
water alone.

SCORING SYSTEM:
Dermal responses were evaluated according to the scheme devised by DRAIZE JH (1959) Dermal Toxicity. Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, p46-59 (see below). For each rabbit and at each exposure time, the score is the mean of the readings made on the two test sites.

Irritation parameter:

other:

Basis:

mean

Remarks:

(3 rabbits)

Time point:

other: 3 minutes exposure

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Moderate to severe dermal effects

Irritation parameter:

other:

Basis:

mean

Remarks:

(3 rabbits)

Time point:

other: 1-hour exposure

Remarks on result:

other: corrosive effects

Irritant / corrosive response data:

After 3 minutes of exposure, moderate to severe erythema was noted in all animals at the 24, 48 and 72-hour observations. On day 7, glossy skin
with areas of flaking and dryness was observed. These adverse reactions reversed within 14 days. Moderate to severe oedema was noted in all
animals at the 24, 48 and 72-hour readings but cleared at day 7.
After 1-hour of exposure, eschar was noted in all animals at the 24, 48 and 72-hour readings. The eschar was surrounded by blanching and well-
defined or moderate erythema extending up to 4cm beyond the sites. Scattered punctate eschar also surrounded 2 of the treated sites. On day 7,
scabbing was noted over a large area of the treated sites in all animals. Flaking, dry, straw-coloured skin ( possible hyperkeratinisation) surrounded
the skin sites. On day 14, scar tissue considered to be indicative of corrosion and desquamation was noted in all animals. No fur growth was noted.
In all animals, moderate to severe oedema which extended ventrally was noted at the 24, 48 and 72-hour readings. No oedema was noted on days 7
and 14.

INDIVIDUAL DERMAL RESPONSES

3-MINUTE SEMI-OCCLUSIVE APPLICATION

Rabbit n°	69	69	71	71	93	93
Skin reaction	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1 hour	0	0	1 H	0	1H	0
24 hours	3 Bl	4 Oe	4 EMBl	4 Oe	3 Bl	3
48 hours	3 Bl	4 Oe	4 EMBl	3 Oe	3 Bl	3
72 hours	3 Bl	3 Oe	4 EMBl	3 Oe	3 Bl	3
7 days	GsScHyp	0	GsScHyp	0	GsHyp	0
14 days	Fr	0	Fr	0	Fr	0

1-HOUR SEMI-OCCLUSIVE APPLICATION

Rabbit n°	69	69	71	71	93	93
Skin reaction	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1 hour	2	3	2	3	2	3
24 hours	4 EWBlP	4 Oe	4 EWBl	4 Oe	4 EWBlP	4 Oe
48 hours	4 EWBlP	4 Oe	4 EMBl	4 Oe	4 EMBlP	3 Oe
72 hours	4 EWBlP	3 Oe	4 EMBl	4 Oe	4 EMBlP	3 Oe
7 days	ScHyp	0	ScHyp	0	ScHyp	0
14 days	DStFn	0	DStFn	0	DStFn	0

KEY TO CODES FOR ADVERSE DERMAL RESPONSES USED INTABLES

Bl Blanching of the skin

D Desquamation

E Eschar

Fn no fur growth

Fr Reduced regrowth of fur

Gs Glossy skin

H Slight haemorrhage of dermal capillaries

Hyp Flaking, dry, straw-coloured skin, (possible hyperkeratinisation) surrounding site

M Moderate erythema extending up to 4cm beyond the site

Oe Oedema extending beyond the site

P Scattered punctuate eschar surrounding site

Sc Scabbing over large area of site

St Scar tissue indicative of corrosion

W Well-defined erythema extending up to 4 cm beyond the site

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Corrosive effects were noted in all the 3 tested animals after a 1-hour exposure period to the test material. According to the criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to classification, packaging and labelling of dangerous substances, the test material is classified Corrosive with the symbol C and the risk phrase R34
" Cause burns".

Executive summary:

Materials and methods

According to OECD 404 (1981), 3 rabbits were exposed to 0.5 ml of Amine, N- tallow alkyltrimethylenedi-. 24 hours before treatment the dorsal fur was shaved with electric clippers exposing approximately 2.5 cm x 2.5 cm of skin. Prior to test substance administration the animals where physically examined and if the shaved area of the skin was normal. 0.5 ml of test substance was applied to one flank using a gauze patch held in place by a non-irrtating semi-occlusive dressing and a restraining bandage. The animals were exposed for 3 minutes 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. As no corrosive effects were observed after this exposure period, the same animals were exposed to the test material for one hour.

Results and discussion

After 3 minutes of exposure, moderate to severe erythema was noted in all animals at the 24, 48 and 72-hour observations. On day 7, glossy skin with areas of flaking and dryness was observed. These adverse reactions reversed within 14 days. Moderate to severe oedema was noted in all animals at the 24, 48 and 72-hour readings but cleared at day 7.

After 1-hour of exposure, eschar was noted in all animals at the 24, 48 and 72-hour readings. The eschar was surrounded by blanching and well-defined or moderate erythema extending up to 4cm beyond the sites. Scattered punctate eschar also surrounded 2 of the treated sites. On day 7, scabbing was noted over a large area of the treated sites in all animals. Flaking, dry, straw-coloured skin ( possible hyperkeratinisation) surrounded the skin sites. On day 14, scar tissue considered to be indicative of corrosion and desquamation was noted in all animals. No fur growth was noted.

In all animals, moderate to severe oedema which extended ventrally was noted at the 24, 48 and 72-hour readings. No oedema was noted on days 7 and 14.

Conclusion

Amine, N- tallow alkyltrimethylenedi- resulted in corrosive effects when applied to the intact rabbit skin for 1 hour

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:

A total of 11in vivostudies on rabbit skin are available to evaluate the potential for skin irritation and corrosion of Diamine C16-18, C18-unsaturated (“tallow-diamine”). Of these, 6 studies were performed with Diamine C16-18, C18-unsaturated itself, of which 4 were not considered as the test substance was not clearly described and it could possibly be formulations.

Additionally, there is data from series of highly reliable GLP studies that were performed together over the category of alkyl-diamines. (Also see ‘Justification in support of cross-reading between Diamines’, document Support Cross-reading - Diamines Final 20131220.pdf attached to IUCLID chapter 13)

 

Alkyl chain	Study	Physical state	Corrosion/irritation
Oleyl	7173-62-8, Acute toxicity: oral_liquid, Haist 2008	liquid	Corr.1B (3 min exposure)
Oleyl	7173-62-8 Acute toxicity: oral_paste, Haist 2008	liquid/ paste	Corr.1B (3 min exposure)
C12-14	90640-43-0, Acute toxicity: oral. Haist 2008	liquid/ paste	Corr.1B (3 min exposure)
Coco	61791-63-7, Acute toxicity: oral. Haist 2008	liquid	Corr.1B (3 min exposure)
HT	68603-64-5, Acute toxicity: oral. Haist, 2008	solid	Irritant
Tallow	61791-55-7, Skin irritation / corrosion, Guest, 1987 61791-55-7, Skin irritation / corrosion, Guest, 1989	paste	Corr.1B (1 hr exposure)

 

For corrosive properties, a relation can be observed with chain length and level of unsaturation: The corrosive effects become less with increasing lengths of alkyl chains, and related with increasing levels of unsaturation. The available data suggests that all diamines based on saturated alkyl chains below C₁₆, and hose of longer chains with a high level of unsaturation should be classified as corrosive to skin. Only HT-diamine, consisting of fully saturated longer alkyl chains of C_16-18is classified as category 2 skin irritant. Testing showed the substance to be a severe irritant (even eschar formation was observed in all treated animals), but not corrosive.

 

There are two studies available that both indicate Diamine C16-18, C18-unsaturated (“tallow-diamine”) to be corrosive after 1 hour exposure to the rabbit skin. A third study available on this substance only involved the evaluation of 3 minute exposures, after which no corrosion was observed.

 

Eye irritation:

Due to the corrosive response 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:

There is no study on respiratory irritation available forDiamine C16-18, C18-unsaturated.

Diamine C16-18, C18-unsaturated is a paste with a mp of 37°C, with a vapour pressure less than 0.0015 Pa at 20°C (value based on read-across from shorter chain C_12-14-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

Available data indicate corrosive properties following exposures of 1 hour and longer. Following exposures, 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 less than 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.