1-nitroguanidine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 1984 - April 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EPA 560/6-82-001

Deviations:

yes

Remarks:

(The rabbits were weighed on 3 October instead of 2 October. This had no effect on the results of the study. )

GLP compliance:

yes

Remarks:

GLP Study Report

Test material

Test material information

Constituent 1

Reference substance name:

1-nitroguanidine

EC Number:

209-143-5

EC Name:

1-nitroguanidine

Cas Number:

556-88-7

Molecular formula:

CH4N4O2

IUPAC Name:

N-nitroguanidine

impurity 1

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

Na2O4S

IUPAC Name:

disodium sulfate

impurity 2

Reference substance name:

Sodium nitrate

EC Number:

231-554-3

EC Name:

Sodium nitrate

Cas Number:

7631-99-4

Molecular formula:

HNO3.Na

IUPAC Name:

sodium 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:

6-amino-1,3,5-triazine-2,4(1H,3H)-dione

EC Number:

211-456-7

EC Name:

6-amino-1,3,5-triazine-2,4(1H,3H)-dione

Cas Number:

645-93-2

Molecular formula:

C3H4N4O2

IUPAC Name:

6-amino-1,3,5-triazine-2,4(1H,3H)-dione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Test substance supplier Sunflower AAP

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elkhorn Rabbitry, Watsonville, CA; U.S.A.
- Age at study initiation: young adults
- Weight at study initiation: 3.2-3.6 kilograms
- Housing: individually in stainless steel, screenbottomed, battery-type cages with automatically flushing dump tanks
- Diet: 150 g/d Certified Purina Chow Diet 5322 (Ralsotn Purina Company, St.Loius, MO)
- Water (e.g. ad libitum): tap water
- Acclimation period: for 5 days prior to testing following a 14 day quarantine, during this period they were observed daily for signs of illness

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-20.0 °C
- Humidity (%): 40-70%
- Air changes (per h): no data
- Photoperiod (hrs dark/hrs light): 12/12


IN-LIFE DATES: From: 06/09/1984 To: 09/10/1984

Test system

Type of coverage:

occlusive

Preparation of test site:

other: close-clipped

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g


VEHICLE
- Amount applied: enough to moisten 0.5 g of Nitroguanidine and form a thick paste
- Concentration of saline solution: 0.9%
- Lot/batch no.: 8C865AY

Duration of treatment / exposure:

4 hours

Observation period:

1 hour and 24, 48 and 72 h after treatment

Number of animals:

eight (four male and four female rabbits)

Details on study design:

TEST SITE
- Preparation of test site: backs were pre-clipped 4 days before dosing and then close-clipped 24 hours before actual dosing
- Area of exposure: back; the clipped area was devided into 4 qaudrants designated I, II, III, and IV
- Site I: vehicle control site
- Sites II and III: test compound sites
- Site IV: sham patch site
- % coverage:
- Type of wrap if used: gauze patch which was taped (semi-impervious hypo-allergenic surgical tape) to the appropriate site; Vet Wrap was then wrapped securely around the animal


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h
- test substance was removed, the skin was wiped if the material adhered


SCORING SYSTEM: see table 1

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

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 30-60 min

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 30-60 min after treatment

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- no irritation/corrosion occured (see table 2)

Other effects:

Rabbit number 570 had multiple small (1 mm) pustules ventral to the patch area at 48 and 72 h after dosing. These lesions were positive for Staphylococcus aureus on bacteriological culture. The test area was not involved.

Any other information on results incl. tables

Table 2: Summary of Primary Irritation Test Data

	30-60 min			24 h			48 h			76 h
Animal No.	Test	Sham	Vehicle	Test	Sham	Vehicle	Test	Sham	Vehicle	Test	Sham	Vehicle
570	0	0	0	0	0	0	0	0	0	0	0	0
571	0	0	0	0	0	0	0	0	0	0	0	0
572	0	0	0	0	0	0	0	0	0	0	0	0
573	0	0	0	0	0	0	0	0	0	0	0	0
574	0	0	0	0	0	0	0	0	0	0	0	0
575	0	0	0	0	0	0	0	0	0	0	0	0
577	0	0	0	0	0	0	0	0	0	0	0	0
578	0	0	0	0	0	0	0	0	0	0	0	0
Mean*	0	0	0	0	0	0	0	0	0	0	0	0
Net Mean Score t	0	0	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Nitroguanidine is not irritating under the conditions of this assay.

Executive summary:

This study has been performed in compliance with Good Laboratory Practice (GLP). The study has been conducted according to US EPA Guideline 560/6-82-001, adopted August 1982.

A gauze patch with 0.5 g of test material (Nitroguanidine), moistened with 0.9% (w/v) physiol. saline, was placed on the clipped skin of four male and female New Zealand White rabbits and closely covered withgauze patch which was taped (semi-impervious hypo-allergenic surgical tape) to the appropriate site. Then Vet Wrap was wrapped securely around the animals. Total exposure duration was four hours. The control site was treated with physiol. saline only and covered analogically.

The animals were checked daily for mortality and systemic symptoms. Body weights were recorded four days prior to testing, at study initiation, and five and eight days after treatment. Skin reactions were evaluated 1, 24, 48, and 72 h after removing the patches according to the scoring system in table 1.

The test-compound was non-irritating. Neither erythema, edema, nor any other recognisable skin reactions were detected at 1, 24, 48 or 72 h after dosing or during the remaining period before terminal sacrifice 14 days after dosing.