Perhydro-1,3,5-trinitro-1,3,5-triazine

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Standard study according to the GLP.

Data source

Materials and methods

Principles of method if other than guideline:

The present study was conducted to evaluate the primary dermal toxicity in rabbits of RDX following a single dermal application of 2 g/kg.
The study was conducted in two parts. The first part tested five rabbits of each sex. On the basis of the results, five additional males were tested.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals were obtained from two suppliers : 13 males and 13 females were received from Lesser's Rabbitry, Union grove, WI and 8 males were received from Dutchland Laboratories, Inc, Denver, PA.
- Age at study initiation: no data
- Weight at study initiation: Radom body weights recorded within three days after arrival were 2.15 +/- 0.25 kg for the rabbits of both sexes of the first shipment and 1.5 +/- 0.1 kg for the males from the second shipment.
- Fasting period before study: no data
- Housing: Each rabbit was housed individually in a stainless steel cage which conformed to the upper weight range. All animals were transferred to clean cages weekly. Alfalfa pellets were placed in the pan bellow the stainless steel mesh floor of the cage to absorb liquids.
- Diet and water (e.g. ad libitum): Purina rabbit chow and tap water were provided ad libitum from arrival until termination.
- Acclimation period: The animals were quarantined for 14 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25°C
- Humidity (%): ambiant relative humidity
- Air changes (per hr): air-conditioned (air change not determined)
- Photoperiod (hrs dark / hrs light): 12 hr light / 12 hr dark cycle

IN-LIFE DATES: No data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

A sufficient quantity of RDX was suspended in 1% carboxymethylcellulose to a final concentration of 800 mg/mL (80% w/v)

Details on dermal exposure:

TEST SITE
- Area of exposure: 12 x 20 cm surface area
- % coverage: no data
- Type of wrap if used: the test area was covered with gauze, plastic film and a lint-free cotton towel.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): All wrapping were removed from the animal 24 hours following application and the skin was washed clean of excess test article with distilled water and dried with a gauze pad.
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Constant volume or concentration used: yes/no
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
TEST SITE
- Area of exposure:
- % coverage:
- Type of wrap if used:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g/kg
- Concentration (if solution): 800 mg/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no data

VEHICLE
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data

Duration of exposure:

24 hr

Doses:

2 g/kg

No. of animals per sex per dose:

First group: 13 males and 13 females
Second group: 8 males

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed: pharmacologic and toxicologic signs.

Statistics:

No data available.

Results and discussion

Mortality:

All 5 females and 3 males from the first part of the study and all 5 males from the retest group of rabbits survived the 14 day observation period.
2 males from the first group were found dead on Test Day 3 and 9, respectively, following slight body weight loss without clinical signs of toxicity.

Clinical signs:

other: No clinical signs of toxicity were observed.

Gross pathology:

No gross pathology was observed.

Other findings:

No data available.

Any other information on results incl. tables

Necropsy findings included scattered multiple gray foci, 1 mm diameter, on all liver lobes for both animals and dark red mucosa of the ileum and dark red contents in the cecum for the male found dead on Test Day 9. Based upon gross necropsy lesions and confirmed by microscopic examination by presence of Bacillus piliformis, Tyzzer's Disease was diagnosed.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A single 2 g/kg dermal application of RDX did not appear to be lethal in rabbits.
The 2 male rabbits which died during the observation period demonstrated Tyzzer's Disease upon pathologic examination.
This disease process and not RDX was apparantly responsible for their deaths.