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Repeated dose toxicity: dermal

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short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This report is a review of the existing literature about the toxicology of RDX. Limited study summary. Study run to a reliable method but not to GLP and no guideline followed.

Data source

Reference Type:
Report Date:

Materials and methods

Test guideline
no guideline followed
Principles of method if other than guideline:
RDX was applied to the clipped backs in doses of 1 or 0.1 mL to 6 rabbits per mixture of RDX/solvent and volume 5 day/week for 4 weeks.
GLP compliance:
Limit test:

Test material

Test material form:
solid: crystalline
Details on test material:
No complementary data available.

Test animals

not specified
not specified

Administration / exposure

Type of coverage:
other: DMSO, acetone, cyclohexanone
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
5 day/week
Doses / concentrationsopen allclose all
Doses / Concentrations:
165 mg/kg/day in DMSO
nominal per unit body weight
Doses / Concentrations:
37.5 mg/kg/day in cyclohexanone
nominal per unit body weight
Doses / Concentrations:
27 mg/kg/day in acetone
nominal per unit body weight
No. of animals per sex per dose:
6 rabbits per dose group
Control animals:
yes, concurrent vehicle

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The repeated doses (daily 5 days/week for 4 weeks) of RDX in DMSO produced no gross evidence of cutaneous irritation throughout the 30 -day observation period. Although no gross effects could be seen, a death occurred after the eighth application of the 1 mL dose of RDX in cyclohexanone (10th day of test), one death after the fifth application of the 0.1 mL dose of RDX in acetone (7th day), and another death after the 10th application of 1 mL dose of RDX in acetone (13th day).

Pathological findings:

Lesion which could be attributed to the compounds tested were confined to the site of application.

When skin was affected, it was often reddened or thickened and there was microscopic evidence of inflammation.

When minimal dermatitis occured in animals that received the mixtures, there was dermatitis of a similar degree in the corresponding solvent control animal, with these exceptions. The animals treated with either 1, 10, or 20 1 mL doses of RDX in DMSO consistently had dermatitis at the time of necropsy while those receiving the same dose of DMSO alone did not. Two rabbits that received one 1 mL dose of RDX in acetone and two that received 20 1 mL doses of RDX in cyclohexanone had dermatitis and the solvent control did not.

No lesions were found in the livers, kidneys, spleens, lungs, tracheas, hearts, intestines, bladders, muscles, bones, or bones marrows of the rabbits which died or were sacrified following repeated topical applications of RDX in the three solvents, or the solvents alone. Gross examination of eyes revealed no cataracts.

When presented for sacrifice and necropsy, three animals had signs of posterior leg weakness or posterior lef paralysis (possibly attributed to broken backs). They had been treated with 5 1 mL doses of RDX (33% in DMSO).

The most serious hazard incident to handling the test solutions appears to be that of repeated skin contact with 5.4% RDX in acetone (2 deaths) and 7.5% RDX in cyclohexanone (1 death).

Applicant's summary and conclusion

According to these results, RDX induce no more damaging than the solvents alone in a repeated dermal exposure in rabbits.