N-C16-18-alkyl-(evennumbered) C18 unsaturated) propane-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:

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

629-719-3

Cas Number:

1219010-04-4

Molecular formula:

Unspecified molecule and hence no molecular formula

IUPAC Name:

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

Details on test material:

- Name of test material (as cited in study report): DIAMINE BG (supplied by Kenobel AB)
- Physical state: off-white solid
- Analytical purity: not stated
- Impurities (identity and concentrations): not stated
- Lot/batch No.: B30/87
- Storage condition of test material: room temperature
- Remark: The test material had a very low melting point and was found to liquify at body temperature.

Test animals

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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