Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

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

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Proposed Health effects test standards for toxic substances control act test rules subpart C. Acute and subchronic health effects 40CFR, Part 722. 44067
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Analytical purity: 91 +/- 2.9% (HPLC)
- Impurities (identity and concentrations): 5-10% of HMX (concentration not determined) and other impureties were not dermined
- Composition of test material, percentage of components: no data
- Isomers composition: not concerned
- Purity test date: no data
- Lot/batch No.: HOL 435-37
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: RDX was stored at the IITRI Kingsbury Ordnance Plant (KOP) Explosive Facility, La Porte, IN at ambiant room temperature and humidity, and in the dark. Approximately 30 g reserve samples were taken and stored under similar conditions as the batches.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals 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

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
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:
No clinical signs of toxicity were observed.
Body weight:
A transient decrease in body weight values was evident for most of the animals on Test Day 3.
By the end of observation period, the surviving animals showed body weight gain.
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.