Oxydiethylene dinitrate

Acute Toxicity: dermal

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 guideline

Test guideline 1

Qualifier:

according to guideline

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

Test guideline 2

Qualifier:

according to guideline

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

Test material information

Constituent 1

Reference substance name:

Oxydiethylene dinitrate

EC Number:

211-745-8

EC Name:

Oxydiethylene dinitrate

Cas Number:

693-21-0

Molecular formula:

C4H8N2O7

IUPAC Name:

2-[2-(nitrooxy)ethoxy]ethyl nitrate

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 or test system 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:

other: 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

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.