Guanidinium thiocyanate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Remarks:

Data are included only to justify the read-across approach of the dossier

Adequacy of study:

supporting study

Study period:

1984-06-21 to 1984-07-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Reference 2

Reference Type:

publication

Title:

Ocular and Dermal Toxicity of Guanidine Nitrate

Author:

Korte D W et al

Year:

1993

Bibliographic source:

International Journal of Toxicology, Vol. 12, No. 6, p.592-593

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Health effects test guidelines, August 1982, EPA 560/6-82-001

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Guanidine nitrate

IUPAC Name:

Guanidine nitrate

Constituent 2

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

Details on test material:

- Name of test material (as cited in study report): Guanidine Nitrate
- Substance type: pure active substance
- Physical state: white crystalline powder
- Analytical purity: 99.99 %
- Lot/batch No.: 123820
- Expiration date of the lot/batch: not available
- Stability under test conditions: stable in acqueous solution (20 μg/ml) at room temperature for
at least 12 days

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
- Weight at study initiation: 2.7 to 3.7 kg
- Housing: individually in steel wire bottem cages in racks equipped with automatically flushing dumptanks
- Diet: approximately 150 g of Certified Purina Rabbit Chow Diet 5322 (Ralston Purina Company, St. Louis, MO)
- Water ad libitum: provided by continous drip from a central line
- Acclimation period: 25 days
- Earmite prevention during acclimation: one application of Canex mineral oil (Pitman-Moore, Inc., Washington Crossing, NJ)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22
- Humidity (%): 50 to 66 with ocasional spike sduring room cleaning
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1984-06-21 To: 1984-07-31

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: 300 cm²
- Type of wrap if used: Vetrap® bandaging tape (Animal Care Products, 3M Corp., St. Paul, MN)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiping with a piece of gauze moistened with 0.9 % saline
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6.19 to 7.49 g in 10 ml of vehicle
- Constant volume used: yes
- For solids, paste formed: yes

VEHICLE
- Amount applied (volume with unit): 10 ml
- Concentration (if solution): 0.9 % sodium chloride (USB, Travenol Laboratories, Inc., Deerfield, IL)
- Lot/batch no. (if required): Lot No. 7C50X0, Expiration date . October 1985

Duration of exposure:

24 hours

Doses:

limit dose at 2000 mg / kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: weeky
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (systemic and dermal), body weight, histopathology

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured during the study.

Clinical signs:

other: Systemic: None of the clinical systemic signs were interpreted as signs of toxicity attributable to the test compound. Dermal: Signs associated with dermal toxicity included erythema, edema, and necrosis, dermal irritation was scored at 1/2, 24, 48. and

Gross pathology:

No deaths occured during the study. Guanidine Nitrate did not produce pathological changes observable at necropsy. Sections of treated and control skin were examined microscopically and no treatment-related lesions were found.

Other findings:

Guanidine Nitrate was a dermal irritant under conditions of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained after a single dermal administration, the dermal LD50 of Guanidine Nitrate was determined to be > 2000 mg/kg bw. No animal died. No clinical signs or gross pathological findings were observed which would indicate systemic toxicity. Body weight was not influenced by the treatment.

Executive summary:

In an acute dermal toxicity study according to the Health effects test guideline, August 1982, EPA560/6-82-001, 5 male and 5 femaleyoung adult New Zealand White rabbits were dermally exposed to guanidine nitrate (99.99 % a.i) in 0.9 % sodium chloride solution for 24 hours to approx. 300 cm² of body surface area at a dose of 2000 mg/kg bw under an semiocclusive dressing.  Animals then were observed for14days.

 

Dermal LD₅₀      Combined =   > 2000 mg/kg bw

 No mortality occurred in this limit test.There were no treatment related systemic clinical signs, necropsy findings or changes in body weight. Dermal irritation was observed including very slight to moderate erythema and very slight to slight oedema. Symptoms were reversible within the observation period. Necrosis was observed in one male which persist as a scab for the entire 14 days of the study. At terminal necropsysections of treated and control skin were examined microscopically and no treatment-related lesions were found.