Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22.8. - 1.10.1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Acute exposure, dermal toxicity. In: Health effects test guidelines. Washington, DC: EPA, Aug 1982, EPA 560/6-82-001
Deviations:
yes
Remarks:
See Overall remarks
Qualifier:
according to
Guideline:
other: Acute dermal toxicity study. LAIR Standard Operating Procedure OP-STX-30, Letterman Army Institute of Research, Presidio of San Francisco, CA. 18 May 1984
Deviations:
yes
Remarks:
See Overall remarks
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diethyleneglycol dinitrate (DEGDN)
- Physical state: pale yellow liquid
- Analytical purity: 96.6%
- Impurities (identity and concentrations): not identified
- Stability under test conditions: stable

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elkhorn Rabbitry, 5265 Starr Way, Watsonville, CA95076
- Age at study initiation: Young Adults
- Weight at study initiation: 2.56 - 2.72 kg
- Housing: individually in stainless steel wire mesh cages in racks equipped with automatic flushing dumptanks, no bedding was used.
- Diet (e.g. ad libitum): approximately 150 g per day of Purina Certified Rabbit Chow No. 5322 (Ralston Purina Company, St Louis, MO)
- Water (e.g. ad libitum): from central line
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8-24.4*C
- Humidity (%): 43 - 56%, except for occasional spikes to 68% during room cleaning.
- Photoperiod (hrs dark / hrs light): 12 hours of light per day

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 8x8 in. (20x20 cm)
- Type of wrap if used: gauze dressing, hypoallergenic tape and bandaging tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposed area was gently wiped with a piece of saline-moistened gauze.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.76 - 3.99 ml
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations and weighting:
- systemic observation: 3 times during the first 6 hours after dosing and daily for the remainder of the study
- dermal observation: the exposed area was examined and scored 1/2, 24, 48, and 72 hours after patch removal and then daily if lesions persisted.
- weighting: weekly
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality.
Clinical signs:
No systemic signs clearly attributable to the compound were observed in any of the animals.
The only systemic signs observed during the study were:
- slight diarrhea (2 animals) - occurred at the very end of the study in both animals and was probably not related to the test compound
- nasal discharge (1 animals) - is characteristic of rabbit pasteurellosis (snuffles)
- curly new hair growth (6 animals) - is probably no more than an incidental finding, but it remains an intriguing observation

Slight erythema was observed initially in 3 of 10 rabbits after removal of wrappings This erythema persisted for 1-3 days. The pattern of the erythema suggested that it may have been due to the wrapping procedure.
Body weight:
Weight gains were not affected by administration of DEGDN.
Gross pathology:
No gross or microscopic findings. These minimal toxicological findings are consistent with the observation that significant quantities of test compound remained on the back after the 24-hr exposure.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A limit dose of 2 g/kg of neat diethyleneglycol dinitrate (DEGDN) was not toxic to rabbits following a 24-hr dermal exposure. DEGDN possesses a minimal potential for acute dermal toxicity.
Executive summary:

The acute dermal toxicity of diethyleneglycol dinitrate, DEGDN, was evaluated in male and female New Zealand White rabbits. Neat DEGDN was applied topically to the clipped dorsal skin surface under a semi-occlusive wrap for 24 hours. A limit dose of 2 g/kg did not produce deaths or clinical (systemic or dermal) signs, during the two-week observation period, that could be directly attributed to administration of the DEGDN. One intriguing observation was the occurrence of curly new hair growth on 6 of the 10 rabbits in the area where DEGDN had been applied.