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Toxicological information

Acute Toxicity: dermal

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988
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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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:
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 72 hr for edema and erythema. The most notable sign of dermal irritation was erythema, which was apparent on all animals at the ½ hr observation. By 72 hr, the erythema had disappeared in all but two rabbits. Edema occurred in two of the animals at the ½ hr observation, three animals at the 24 hr observation and no animal at the 48 hr observation. Necrosis was the most serious dermal reaction. On one male, the necrotic area was 2 cm in diameter and persisted as a scab for the entire 14 days of the study.
Body weight:
Dermal administration of Guanidine Nitrate had no effect on body weight.
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.