Diguanidinium carbonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1998-07-21 to 1999-01-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline-conform study performed under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diguanidinium carbonate

EC Number:

209-813-7

EC Name:

Diguanidinium carbonate

Cas Number:

593-85-1

Molecular formula:

CH5N3.1/2CH2O3 (one guanidine species, as denoted in the ESIS database) CH5N3.CH5N3.CH2O3 (as in the crystalline from, basis for the molecular weight 180.1658 g/mol as given below)

IUPAC Name:

bis(amino(imino)methanaminium) carbonate

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): Guanidine Carbonate Pure
- Substance type: Salt with organic kation and inorganic anion
- Physical state: White crystalline powder
- Analytical purity: 99.7 %
- Impurities: Sulphate ash <0.05 %, heavy metals calculated as lead, <10 ppm (mg/L), iron 1 ppm, lead <1 ppm, arsenic <3 ppm
- Purity test date: 1998-06-09
- Lot/batch No.: 1867 of Agrolinz Melamin GmbH, St.-Peter-Strasse 25, A-4021 Linz
- Expiration date of the lot/batch: Not specified but considered stable under conditions of storage for at least 5 years
- Storage condition of test material: At room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: J. Schitkovits, A-2620 Natschbach.
- Age at study initiation: not reported
- Weight at study initiation: 2.5 - 2.9 kg
- Housing: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm x 35 cm.
- Diet (e.g. ad libitum): Altromin 2023 diet for rabbits, ad libitum. Random samples of the feed are analysed for contaminants by Altromin, D-32791 Lage.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 (average)
- Humidity (%): 60 (average)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: The hair was clipped on the dorsal area of the trunk one day before the application.

Vehicle:

water

Remarks:

Samples of the test item were moistened with distilled water.

Controls:

other: Surrounding untreated skin was taken as a control area.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): Samples of the test item were moistened with distilled water.

Duration of treatment / exposure:

4 hours

Observation period:

3 days. Observations were made 1, 24, 48 and 72 hours after patch removal.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- Type of wrap if used: The test item samples were placed on cellulose patches (pure Zellin swap, Hartmann, Wiener Neudorf) and fixed marginally (Blenderm R surgical tape, hypoallergenic 3M). The application sites were covered semi-occlusive by dressing (self adhesive non woven fabric, hypoallergenic, Beiserdorf)

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test item was removed with wet Kleenex tissues, if necessary
- Time after start of exposure: After 4h exposure (Thus the duration of the exposure was 4 hours.)

SCORING SYSTEM:
Erythema / Eschar formation
0: No erythema.
1: Very slight erythema (barely perceptible).
2: Well-defined erythema.
3: Moderate to severe erythema.
4: Severe erythema (beet redness) or eschar formation (injuries in depth).
Oedema formation
0: No oedema.
1: Very slight oedema (barely perceptible).
2: Slight oedema (edges of area well defined by definite raising).
3: Moderate oedema (raised approximately 1 mm).
4: Severe oedema (raised more than 1 mm and extending beyond area of exposure).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

4

Any other information on results incl. tables

No general toxic effects were noted and all areas treated with the test substance and all control areas were normal before the

application and at each observation time.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance Guanidine carbonate did not cause any adverse skin reactions in this study.

Executive summary:

The aim of this study was to investigate possible irritation or corrosion by the test substance following a single application to the intact skin of New Zealand White rabbits. Methods and investigations were performed in conformance with the OECD TG 404.

Approximately 0.5 g Guanidine carbonate, moistened with distilled water, was applied via a patch to an area of about 2.5 cm x 2.5 cm of the intact skin of each of 3 rabbits and covered by semi-occlusive dressing. The duration of the exposure was 4 hours.

The body weight was measured at the start and at the termination of the test. The animals were observed for general signs of toxicity once daily and the skin was examined 1, 24,48 and 72 h after patch removal.

No general toxic effects were observed. All exposed skin sites were normal at each examination term. In all animals mean scores for erythema as well as for oedema formation, calculated from the examinations performed 24,48 and 72 hours after patch removal, were "0", i.e. normal. The test substance did not cause any adverse skin reactions in this study.