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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

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:
Study performed before the implementation of the REACH regulation

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyl 4,4-bis(tert-butyldioxy)valerate
EC Number:
213-626-6
EC Name:
Butyl 4,4-bis(tert-butyldioxy)valerate
Cas Number:
995-33-5
Molecular formula:
C17H34O6
IUPAC Name:
butyl 4,4-bis(tert-butylperoxy)pentanoate
Test material form:
other: colorless liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, 76410 Saint-Aubin-lès-Elbeuf, France
- Age at study initiation: 1-3 months old
- Weight at study initiation: 358 ± 12 g for the males and 371 ± 17 g for the females
- Housing: housed individually in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm)
- Diet: free access to 106 pelleted diet (SAFE, Villemoisson, Epinay sur-Orge, France)
- Water: water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr):12
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
25%
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Day(s)/duration:
Day 8
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
50%
Day(s)/duration:
Day 22
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Test group: 20
Negative control group: 10
Details on study design:
RANGE FINDING TESTS:
Tested concentrations:
By intradermal route: 25%, 10% and 5% (w/w)
By cutaneous route: 100% and 50% (w/w)
Challenge controls:
The vehicle was applied under the same experimental conditions to the skin of the posterior left flank.
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole

Results and discussion

Positive control results:
Mercaptobenzothiazole induced positive skin sensitization reactions in 100% (10/10) guinea pigs

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10

Any other information on results incl. tables

- Clinical examinations:

No clinical signs and no deaths were observed during the study.

- Body weight:

The body weight gain of the treated animals was similar to that of the control animals

- Challenge phase - Scoring of cutaneous reactions

No relevant cutaneous reactions were observed.

Only a discrete erythema (grade 1) and/or dryness of the skin were noted on one or two flanks of a few animals of both groups.

These very slight cutaneous reactions, which were observed in only a few animals of both groups and as well on the flank receiving the test substance as on the flank receiving the vehicle,

were not attributed to delayed contact hypersensitivity.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to the maximization method of Magnusson and Kligman, LUPEROX 230M50 does not induce delayed contact hypersensitivity in guinea pigs.
Executive summary:

The potential of LUPEROX 230M50 to induce delayed contact hypersensitivity was evaluated in guinea pigs according to the maximization method of Magnusson and Kligman and to OECD guideline No. 406 and the principles of Good Laboratory Practice Regulations. Thirty guinea pigs were allocated to two groups: a control group of five males and five females and a treated group of ten males and ten females. On day 1, three pairs of intradermal injections were performed in the interscapular region of all animals:

. Freund's complete adjuvant (FCA) diluted at 50% (v/v) with 0.9% NaCl (both groups), test substance at 25% (w/w) in corn oil or vehicle alone (control group),

. test substance at 25% (w/w) in a mixture FCA/0.9% NaCl 50150 (v/v) (treated group) or vehicle at the concentration of 50% (w/v) in a mixture FCA/0.9% NaCl 50150 (v/v) (control group).

On day 8, the undiluted test substance (treated group) or the vehicle (control group) was applied topically to the same test site, which was then covered by an occlusive dressing for 48 hours.

On day 22, all animals of the treated and control groups were challenged by a cutaneous application of the test substance at 50% (w/w) in corn oil to the right flank. The left flank served as control and received the vehicle only. Test substance and vehicle were maintained under an occlusive dressing for 24 hours. Skin reactions were evaluated approximately 24 and 48 hours after removal of the dressing.

At the end of the study, animals were killed without examination of internal organs. No skin samples were taken from the challenge application sites.

No clinical signs and no deaths were noted during the study. No well-defined cutaneous reactions were observed after the challenge application.

According to the maximization method of Magnusson and Kligman, the test substance LUPEROX 230M50 does not induce delayed contact hypersensitivity in guinea pigs.