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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 17 July to 10 August 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study run to a reliable method but not to GLP and no guideline followed
Qualifier:
no guideline followed
Principles of method if other than guideline:
The maximisation test comprises 2 procedures. The induction procedure consists of an intradermal injection of the test material followed after 7 days by a topical application. The challenge procedure, which consists of a topical application is carried out 21 days after commencement of the induction procedure.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Porcellus Animals Limited
- Weight at study initiation: 350-400 g
- Housing: For each of the 3 tests, 25 test group animals were allocated equally into 5 cages, 10 control group animals were allocated equally in 2 cages and 2 dose finding animals were housed in a single cage. The cages had a grid floor beneath which was a peat moss filled tray.
- Diet (e.g. ad libitum): The animals were fed on BP Nutrition FD1 Diet, supplemented with hay. They were allowed food ad libitum.
- Water (e.g. ad libitum): They were allowed water ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C (extremes of 18°C-24°C)
- Humidity (%): 63% (extremes of 52%-74%)

No additional data
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water in induction procedure and paraffin oil in challenge procedure
Concentration / amount:
Injection phase: 6.67% w/v
Topical induction: 60% w/v
Challenge procedure: 60% and 30% w/v
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water in induction procedure and paraffin oil in challenge procedure
Concentration / amount:
Injection phase: 6.67% w/v
Topical induction: 60% w/v
Challenge procedure: 60% and 30% w/v
No. of animals per dose:
25 guinea pigs
Details on study design:
RANGE FINDING TESTS: A maximum non-irritant concentration of test substance, p-Phenylenediamine and sodium lauryl sulphate was determined each in a pair of guinea pigs, hitherto treated with 2 injections of Freunds Complete Adjuvant only. The test materials were applied at a series of concentrations to the shaved flanks of the guinea pigs under the same occlusive patch system used for the topical induction. The test substance was tested at 60% and 30% w/v in paraffin oil.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Once (injection) and once (topical)
- Exposure period: Single injection and topical 48 hours
- Test groups: 6.67% w/v in distilled water in injection phase, 60% w/v in distilled water in topical induction.
- Control group: Positive control: p-Phenylenediamine 2% w/v in distilled water in injection phase and topical induction. Negative control: Sodium lauryl sulphate 1% w/v in distilled water in injection phase and topical induction.
- Site: Scapular region for injection phase and torso for topical induction.
- Frequency of applications: Topical followed one week after injection
- Duration: 3 weeks
- Concentrations: Injection phase: 6.67% w/v, Topical induction: 60% w/v

B. CHALLENGE EXPOSURE
- No. of exposures: Once
- Day(s) of challenge: Two weeks after the topical induction
- Exposure period: 24 h
- Test groups: 60% w/v in paraffin oil
- Control group: Positive control: p-Phenylenediamine 2% w/v in distilled water. Negative control: Sodium lauryl sulphate 0.5% w/v in distilled water.
- Site: Left flank
- Concentrations: 60% w/v
- Evaluation (hr after challenge): 24 hours

No additional data
Challenge controls:
The control guinea pigs which were pre-treated with Adjuvant only at the injection phase, were included to check on the irritancy of the test materials at the challenge concentration.
Positive control substance(s):
yes
Remarks:
p-Phenylenediamine
Positive control results:
After being challenged with p-Phenylenediamine at a concentration of 2% w/v in distilled water, 24/25 test group animals showed moderate and confluent erythema while 1/25 test group animals showed slight erythema.
None of the control group animals showed erythema when challenged with p-Phenylenediamine at a concentration of 2% w/v in distilled water, so supporting the dose ranging results that at that concentration the test material would be non-irritant.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
60% w/v
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 60% w/v. No with. + reactions: 0.0. Total no. in groups: 25.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2% w/v
No. with + reactions:
25
Total no. in group:
25
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 2% w/v. No with. + reactions: 25.0. Total no. in groups: 25.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5% w/v
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5% w/v. No with. + reactions: 0.0. Total no. in groups: 25.0. Clinical observations: None.

Preliminary tests indicated that the test substance should be non-irritant at a concentration of 60% w/v in paraffin oil on adjuvant pre-treated guinea pigs when applied to the shaved flank under occlusion.

The test substance did not elicit positive responses in the test group after challenge of the 25 guinea pigs by topical application.

The test substance was tested at the challenge phase on 10 guinea pigs which were Adjuvant pre-treated only.

None of these irritancy control group animals reacted positively to this topical application, so supporting the dose ranging results that at a concentration of 60% w/v in paraffin oil this test material would be non-irritant.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There was no evidence from the Magnusson-Kligman Maximisation test to suggest that the test substance is a sensitiser in guinea pigs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitisation potential of HMX was investigated in a key study carried out by Inveresk Research Inernational Ltd on behalf of the U.S. Army Medical Research and Development Command. A guinea pig maximisation test was carried out using female albino guinea pigs of the Dunkin-Hartley strain. Groups of 25 guinea pigs were tested with HMX and a positive control substance (p-Phenylenediamine). The induction phase started with an intradermal exposure to HMX and HMX plus adjuvant. Six days after this exposure, an epidermal exposure to HMX was performed. An epicutaneous challenge was then performed at day 21. No indication of sensitisation was obtained.

A supporting study was available (McNamara et al, 1974). Topical or intradermal application of HMX in the solvents (DMSO, cyclohexanone and acetone) 3 days a week for 3 weeks, followed 2 weeks later by topical or intradermal challenge, gave no evidence of sensitisation.


Migrated from Short description of key information:
There was no evidence from the Magnusson-Kligman maximisation test to suggest that HMX is a skin sensitiser.

Justification for selection of skin sensitisation endpoint:
The key study was carrried out in a scientific manner using accepted methods similar to modern international guidelines. Not carried out to GLP or to current international guidelines.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

A Magnusson-Kligman maximisation test in guinea pigs was carried out with HMX. Results were negative. Therefore HMX is not classified as a skin sensitiser.