1-nitroguanidine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 Sep - 10 Oct 1984

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:

other: EPA Office of Pesticides and Toxic Substances (Ts-792); Acute exposure, dermal toxicity. In: Health Effects test guidelines. Washington DC; 1982; EPA 560/6-82-001

Deviations:

yes

Remarks:

The animals were not submitted to necropsy until 15 days after dosing. Animals were observed on the 15th day before being submitted for necropsy. The food for the animals was removed early on the 14th day and was returned later that morning after the next

Principles of method if other than guideline:

according to: Acute dermal toxicity study. LAIR Standard Operation Procedure OP-STX-30, Letterman Army Institute of REsearch, Presidio of San Francisco. 1984

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP study number 84025

Test type:

fixed dose procedure

Limit test:

yes

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

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elkhorn Rabbitry, Watsonville, CA 95076
- Age at study initiation: young
- Weight at study initiation: 2539 - 3900 g
- Housing: individually in stainless steel, wire mosh bottom, battery-type cages with automatic flushing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 19 days (quarantained)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20 C°
- Humidity (%): 50-70 % (spikes up to 85% during room cleaning)
- Photoperiod (hrs dark/hrs light): 12 h/12h

IN-LIFE DATES: From: 25. Sept 84 To: 10. Oct 84

Administration / exposure

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: 300 cm^2
- Type of wrap if used: gauze + hypoallergic tape (Durapore Surgical tape, 3M Corp) + Vetrap bandaging tape (Animal Care products, 3M Corp)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with gauze moistured with water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg
- Concentration (if solution): 0.25 g per ml salino
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2 g/kg

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1, 2, 4 h after dosing and daily for the remainder of the study. A second "walk adjathrough" was performed daily with only significant observations recorded. Dermal observations also were recorded daily according to severity, area, and location.
- Necropsy of survivors performed: yes

Statistics:

not applicable

Results and discussion

Preliminary study:

not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

Female:
84F584 - "[..] lymph nodes were greatly enlarged (up to 9 cm diameter), white and lobular. The nodes contained [..] white creamy material."
84F585 - no lesions recognized.
84F586 - no lesions recognized.
84F587 - no lesions recognized.
84F588 - The skin had a small (2 x 8 cm) area of slight erythema in the midlumber area.

Male:
84F591 - The skin had a small (2 x 3 cm) area of slight erythema in the midlumber area.
84F592 - There was a purulent, bilateral otitis media.
84F593 - The skin had a small (5 x 7 cm) area of slight erythema in the midline, dorsal thoracic area. The kidneys had bilateral tan mottled areas over the entire cortex.
84F594 - no lesions recognized.
84F595 - There was a purulent, bilateral otitis media.

Any other information on results incl. tables

- Both dosed and control skin section contain minimal, small aggregates of macrophages, heterophils and lymphocytes in the superficial dermis and adjacent to hair follicles. Dosed and control skin sections have a few follicles with individual or small groups (3 -6 cells) of necrotic cells in the external root sheath. There was no difference in severity of skin lesions between dosed and control skin sections.

- No compound related lesions and/or deaths were seen. Otitis media was considered an incidential finding.

- Tan, mottled, bilateral areas over the cortex of the kidney may have been caused by Encephalitozoon cuniculi, a commonprotozoen parasite of rabbit kidney.

- The erythema observed grossly in rabbits 84F588, 84F591 and 84F593 could not be directed microscopically and most likely was discoloration on the skin surface rather than erythema.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A limit dose of 2 g/kg of nitroguanidine was not lethal following dermal exposure for 24 hours, and produced no compound-related clinical signs or dermal irritation during the 15 day observation period. Nitroguanidine possesses a minimal potential for acute dermal toxicity.

Executive summary:

In an acute dermal toxicity study according to GLP, groups of New Zealand White Rabbits (5/male, 5/female) were dermally exposed to nitroguanidine (99.4 %) in physiol. saline for 24 h to approximately 300 cm² at a LIMIT dose of 2 mg/kg bw. Animals then were observed for 15 days.

There were no treatment related deaths, clinical signs or necropsy findings. Nitroguanidine possesses a minimal potential for acute dermal toxicity.