Guanidinium nitrate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-06-22 to 1988-06-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Guanidinium nitrate

EC Number:

208-060-1

EC Name:

Guanidinium nitrate

Cas Number:

506-93-4

Molecular formula:

CH6N4O3

IUPAC Name:

amino(imino)methanaminium nitrate

impurity 1

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

water

impurity 2

Reference substance name:

Ammonium nitrate

EC Number:

229-347-8

EC Name:

Ammonium nitrate

Cas Number:

6484-52-2

Molecular formula:

H3N.HNO3

IUPAC Name:

Ammonium nitrate

impurity 3

Reference substance name:

4,6-diamino-1,3,5-triazin-2(1H)-one

EC Number:

211-455-1

EC Name:

4,6-diamino-1,3,5-triazin-2(1H)-one

Cas Number:

645-92-1

Molecular formula:

C3H5N5O

IUPAC Name:

4,6-diamino-1,3,5-triazin-2(1H)-one

impurity 4

Reference substance name:

(4,6-Diamino-1,3,5-triazine-2-yl)guanidine

Cas Number:

4405-08-7

Molecular formula:

C4H8N8

IUPAC Name:

(4,6-Diamino-1,3,5-triazine-2-yl)guanidine

impurity 5

Reference substance name:

Melamine

EC Number:

203-615-4

EC Name:

Melamine

Cas Number:

108-78-1

Molecular formula:

C3H6N6

IUPAC Name:

1,3,5-triazine-2,4,6-triamine

impurity 6

Reference substance name:

Cyanoguanidine

EC Number:

207-312-8

EC Name:

Cyanoguanidine

Cas Number:

461-58-5

Molecular formula:

C2H4N4

IUPAC Name:

1-cyanoguanidine

Test material form:

solid: crystalline

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands.
- Age at study initiation: 12 weeks
- Weight at study initiation: 2065 - 2390 g
- Housing: individually housed in a plastic cage with a perforated floor
- Diet: 100 g per day (LKK-20, diameter 4 mm) of standard laboratory animal diet obtained from Hope Farms, Woerden, The Netherlands
- Water: ad libitum, tap-water (via automatic nozzles):
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 55-75
- Photoperiod (hrs dark / hrs light): 12/12

One day before treatment, the fur was removed from the dorsal flanks of the animals by clipping, exposing an area of the skin of
approximately 10 cm x 10 cm.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Milli-RO water (Millipore Corp., Bedford, Mass., USA)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g, moistened with 0.3 mL Milli-RO water

Duration of treatment / exposure:

4 h

Observation period:

72 h
The exposed skin areas were examined for signs of erythema and oedema and the responses were scored approximately 60 minutes and 24, 48 and 72 hours after removal of the patches.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approx. 6 cm²
- Coverage: Each portion of the prepared test substance was spread on a 6 cm2 patch of Metalline (Lohmann, FRG) and mounted on permeable tape (Micropore, 3M, St.Paul, USA). This was applied to the left flank of each animal, the right flank being covered with the same dressing without test substance.
- Type of wrap used: flexible bandage (Coban, 3M, St. Paul, USA).

REMOVAL OF TEST SUBSTANCE
- Washing: The remaining test substance was removed using a dry tissue and subsequently a tissue moistened with tap-water.
- Time after start of exposure: 4 h

SCORING SYSTEM:

Erythema and eschar formation
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well—defined erythema
3: Moderate to severe erythema
4: Severe erythema (beef redness) to slight 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 millimetre)
4: Severe oedema (raised more than 1 millimetre and extending beyond area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

The treated skin of all three animals was scored for erythema and oedema. The test substance caused no adverse effects to the skin, except very
slight erythema and very slight oedema in one animal 60 minutes after removal of the bandage.

Other effects:

No signs of systemic intoxication were observed in any of the rabbits.

Any other information on results incl. tables

Summary Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Oedema
	Max. score: 4	Max. score: 4
60 min	0/0/1	0/0/1
24 h	0/0/0	0/0/0
48 h	0/0/0	0/0/0
72 h	0/0/0	0/0/0
Average 24h, 48h, 72h	0/0/0	0/0/0
Reversibility	c/c/c	c/c/c
Average time (unit) for reversion	24 h	24 h

Reversibility: c=completely reversible

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Classification is based on erythema/eschar and oedema calculated as mean scores following grading at 24, 48 and 72 hours after removal of the test material, in consideration of reversibility. In this study, the test substance Guanidine Nitrate is considered not to be irritant to the skin according to the criteria of:
- CLP - (EU GHS), Regulation (EC) No. 1272/2008
- OECD GHS (2nd rev. edition, UN, 2007)
- Directive 67/548/EEG .

Executive summary:

In a primary dermal irritation study according to OECD Guideline 404 1981, three White New Zealand rabbits were semi-occlusive dermally exposed to 0.5 g of Guanidine Nitrate for 4 hours to approximately 6 cm² of body surface area. Animals then were observed for 72 hours. Irritation was scored by the method of Draize as stipulated by OECD Guideline 404.

Very slight erythema and oedema was observed in 1/3 animals 60 minutes after patch removal and was fully reversible after 24 hours.

 

No classification for skin irritation is required for Guanidine Nitrate according to CLP, EU GHS (Regulation (EC) No 1272/2008).