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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 1996 until April 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
common method of the time the study is performed

Test material

Constituent 1
Chemical structure
Reference substance name:
3,5,5-trimethylhexanal
EC Number:
226-603-0
EC Name:
3,5,5-trimethylhexanal
Cas Number:
5435-64-3
Molecular formula:
C9H18O
IUPAC Name:
3,5,5-trimethylhexanal
Details on test material:
klare Flüssigkeit
Flüssigkeit erscheint optisch homogen
ph-Wert nicht messbar
Haltbarkeit > 1 Jahr
Reinheit 91,2 Masse-% (Gas-Chromatographie)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Versuchstierzucht, Borchen, Germany
- Microbiological status of animals, when known: healthy
- Age at study initiation: young adults
- Weight at study initiation: under 500 g
- Housing:conventional, maximum 5 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at leat 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 +/- 3 ° C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15-fold/hr
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
maize oil
Concentration / amount:
5% Test material
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
Route:
epicutaneous, occlusive
Vehicle:
maize oil
Concentration / amount:
50% Test material
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10 animals in the main groups and 5 animals in control groups
Details on study design:
RANGE FINDING TESTS:
In the pre-test, a well-tolerated concentration of the test substance, which could be used for the induction phase of the main test, should be determined for intracutaneous administration.
Furthermore, a slight to moderately irritating concentration, which could be used for the induction phase of the main test, was determined for the three applications.
Finally, the maximum non-irritating concentration, which could be used for triggering, should be determined during dermal administration.

MAIN STUDY
A. INDUCTION EXPOSURE
Intracutane Induction (Day 0)
- No. of exposures: 6 injections
- Test groups: 1
- Control group: 2
- Site: shoulder area 2 x 4 cm
- Duration: Evaluation of injection sites after 1 and 24 hr after application
- Concentrations: 5% in vehicle

Dermal Induction (Day 7)
- No. of exposures: one
- Exposure period: 48 hr fixation of the patch
- Test groups: 1
- Control group: 2
- Site: shoulder area 2x4 cm
- Duration: Evaluation of the application site after 49 and 72 hr after application
- Concentrations: undiluted test item

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: Day 21
- Exposure period: Fixation of th epatch for 24 hr
- Test groups:
- Control group:
- Site: flank
- Concentrations: 50% of th etest item in vehicle
- Evaluation (hr after challenge): 24, 48, 72 hr after application

The second challenge was not performed due to the positive result in the first challenge.

Positive control substance(s):
not required
Remarks:
Sensitization testing of the guinea pig strain was performed with 2-mercaptobenzothiazole.

Results and discussion

Positive control results:
no positive control

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% test item in maize-oil
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema and Oedema
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
50% test item in maize-oil
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
erythema in 6 animals; oedema in 3 animals
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
1% 2-MCBT in maize-oil
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
positive skin reactions
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The substance is a sensitiser for skin of guinea pigs.
Executive summary:

TRIMETHYLHEXANAL was tested on guinea pigs in the maximization test according to Manugsson and Kligman for sensitization of the skin.

In order to determine the potentially sensitizing effect of TRIMETHYLHEXANAL, a test group of 10 animals and two control groups of 5 animals each were used for the test. Any reactions, especially erythema and edema formation, were assessed 48 and 72 hours after initiation.

The 50% concentration of the test substance was administered as the maximum concentration in the pretreatment with dermal administration and no signs of systemic toxicity.

For the treatments in the induction phases, the following subdistance concentrations were determined:

- In the case of intracutaneous injection, the test substance was used in corn oil 5%.

- In the case of the dermal treatment in the induction phase II, the test substance was administered undiluted.

- In the release phase, the 50% test substance concentration in maize germ oil was administered as a non-irritating concentration.

In the pre-test, administration of the concentrated test substance to the animals resulted in slight irritation in the form of erythemas and oedemas and dandruff formation on the guinea pig skin. Pretreatment of the skin with 10% sodium dodecyl sulfate (SDS) in vaseline was not necessary.

The dermal induction treatment reactions were evaluated 49 and 72 hours post-application (p.a.):

In this case, the injection sites, which had been treated with a 5% test substance or vehicle a week before, showed 49 and 72 hours of p.a. in all test and / or control animals no irritation. Only in a test animal after 72 hours was the whole application area scraped and strongly bloody. An assessment was not possible. At all injection sites previously treated with 5% test substance preparation in FCA (test animals) and with only FCA (control animals), 49 h p.a. in 8 test and 4 control animals, moderate erythema and edema. Two test animals had severe erythema and edema with scab formation and bloody scabies at these injection sites and 6 control animals severe erythema and edema with scab formation, in two animals with bloody scalp wounds. After 72 hours, all test and 9 control animals in this area showed severe erythema and edema with scab formation, in 5 test animals, and one animal of the control group associated with bloody scratch wounds. 1 control animal at this time had moderate erythema and edema.

The triggering treatment was carried out with the 50% test substance in maize germ oil. The treatment in all test animals led to positive skin irritations in the sense of sensitization in the form of clearly circumscribed erythema and oedema, in 4 animals combined with skin dryness. After 72 hours, p.a. showed 6 animals still light with clear Haurezungen with skin dryness or dandruff formation. Two animals had only dandruff formation and two animals were free of irritation. The animals of the control group had no skin irritations after 48 hours and 72 hours after the treatment with the test substance on the right flank. Treatment of the test and control animals with the vehicle on the left flank also did not result in any irritation on the skin.

Repeated triggering with the second control group was not necessary because of the clear result.