N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2016

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

EC Number:

247-361-2

EC Name:

N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Cas Number:

25952-53-8

Molecular formula:

C8H17N3.ClH

IUPAC Name:

N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide hydrochloride

Test material form:

solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl: KBL (NZW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany,
- Age at study initiation: 19 to 30 weeks
- Weight at study initiation: > 2 Kg
- Housing: Semi-barrier in an air conditioned room. Housed in ABS plastic rabbit cages.
- Diet (e.g. ad libitum): Free access to autoclaved hay and Altromin maintenance diet for rabbits.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): Artificial light (12 hours light/dark cycle)

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Aqua ad injectionem

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test item was applied.

VEHICLE
- Amount(s) applied (volume or weight with unit): Only used to ensure good contact with the test substance and skin.

Duration of treatment / exposure:

Applied over a 4 hour period

Observation period:

Up to 14 days after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Left side of dorsal area
- % coverage: approximately 6 cm3
- Type of wrap if used: the gauze used was held in place with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with tap water after 4 hours of exposure

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1, 24, 48 and 72 hours after patch removal.

SCORING SYSTEM:
- Method of calculation: Scoring and grading as per standard system in relevant OECD guideline.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 11 days

Remarks on result:

other: max score seen in study refers to whole observation period.

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: max score seen in study refers to whole observation period.

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

> 0 - <= 1

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: max score seen in study refers to whole observation period.

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: max score seen in study refers to whole observation period.

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: max score seen in study refers to whole observation period.

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 5 days

Remarks on result:

other: max score seen in study refers to whole observation period.

Irritant / corrosive response data:

The first animal showed irritation effects (erythema and oedema) immediately after patch removal. The subsequent observations revealed signs of irritation (erythema, oedema and eschar formation) within 10 days after removing the patch. Eschar formation was also observed in isolation on day 8.

The examination of the test site showed irritant effects 1 hour after the patch removal in Animal No. 2 (oedema) and animal No. 3 (oedema and erythema). Subsequent observations revealed signs of irritation (erythema, oedema eschar formation and desquamation) within the maximum of the prolonged observation period of 14 days. Eschar formation was observed in animal Nos. 2 and 3 up until Day 13 and 14 of the observation period, respectively.

Other effects:

Minor skin inflammation observed as a result of the adhesive dressing in the first animal. There were also no significant bodyweight changes during the contact and observation period and no relevant clinical signs.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the conditions of the study, the dermal application of the test substance showed irritant but not corrosive effects. The changes were not reversible within the maximum observation period of 14 days in one animal.