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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:
1996-11-14 till 1997-02-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study (OECD 406)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl undec-10-enoate
EC Number:
203-910-8
EC Name:
Methyl undec-10-enoate
Cas Number:
111-81-9
Molecular formula:
C12H22O2
IUPAC Name:
methyl undec-10-enoate
Details on test material:
- Name of test material (as cited in study report): METHYL UNDECYLENATE
- Substance type: organic
- Physical state: colourless liquid
- Analytical purity: 98.3%.
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: 9610002
- Expiration date of the lot/batch:
- Stability under test conditions: no data
- Storage condition of test material: at room temperature and protected from light
- Other:

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Lebeau (78950 Gambais - France)
- Age at study initiation: no data
- Weight at study initiation: 360 ± 14g (males), 349 ± 21g (females)
- Housing: animals were housed individually in polycarbonate cages (48 cm x 27 cm x 20 cm) equipped with a polypropylene bottle. Dust-free sawdust was provided as litter.
- Diet (e.g. ad libitum): During the study, the animals had free access to "106 diet" (U.A.R., Villemoisson-sur-Orge, France).
- Water (e.g. ad libitum): Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least five days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 2 1 ± 2°C
- Humidity (%): 30 - 70 %
- Air changes (per hr): about 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h / 12 h


IN-LIFE DATES: From: 1996-11-14 To: 1996-12-16

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: paraffin oil
Concentration / amount:
Induction (treated group)
- intradermal injections: METHYL UNDECYLENATE at 75% (wlw) in paraffin oil,
- topical application: METHYL UNDECYLENATE undiluted

Challenge (all groups)
- topical application: METHYL UNDECYLENATE undiluted.
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: paraffin oil
Concentration / amount:
Induction (treated group)
- intradermal injections: METHYL UNDECYLENATE at 75% (wlw) in paraffin oil,
- topical application: METHYL UNDECYLENATE undiluted

Challenge (all groups)
- topical application: METHYL UNDECYLENATE undiluted.
No. of animals per dose:
Treated group: 10 males + 10 females (one dose tested only)
Control group: 5 males + 5 females
Details on study design:
RANGE FINDING TESTS:
A preliminary test was conducted in order to determine the concentrations to be tested in the main study. Teh range finding test was conducted via both intradermal route and cutaneous route. For selection of concentrations for the main study, the following criteria were used:
- the concentrations should be well-tolerated systemically and locally,
- intradermal injections should cause moderate irritant effect (no necrosis or ulceration of the skin),
- topical application for the induction should cause at most weak or moderate skin reactions or be the maximal practicable concentration,
- topical application for the challenge should be the highest concentration which does not cause irritant effect.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 (three pairs of sites)
- Exposure period: 10 d
- Test groups: 10 males + 10 females (one dose tested only)
- Control group: 5 males + 5 females
- Site: dorsal region between the shoulders
- Frequency of applications: single application
- Duration: On day 8, a topical application to the region of the intradermal injections (4 cm x 2 cm) was performed, treated group with test item in vehicle, control with vehicle only. The patch was held in contact to the skin for 48 h.
- Concentrations: intradermal injections: METHYL UNDECYLENATE at 75% (wlw) in paraffin oil, topical application: METHYL UNDECYLENATE undiluted


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24 h
- Test groups: 10 males + 10 females
- Control group: 5 males + 5 females
- Site: posterior right flank (vehicle: left flank)
- Concentrations: 0.5 ml of test substance undiluted
- Evaluation (hr after challenge):


OTHER:
Challenge controls:
Freund's complete adjuvant
Positive control substance(s):
yes
Remarks:
2,4-DINITRO CHLOROBENZENE (DNCB)

Study design: in vivo (LLNA)

Statistics:
no statistics applied

Results and discussion

Positive control results:
Under the given experimental conditions and according to the Magnusson and Kligman method, the test substance 2,4-DINITRO CHLOROBENZENE at a concentration of 0.5% (w/w) induced positive skin sensitization reactions in 50% of the guinea-pigs.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 ml
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
5 animals dead, which is attributed to the test substance, however not to hypersensitivity effects
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: 5 animals dead, which is attributed to the test substance, however not to hypersensitivity effects.
Reading:
other: day 5 and day 21
Group:
test chemical
Dose level:
0.5 ml
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
one animal with piloerection and hypoactivity
Remarks on result:
other: Reading: other: day 5 and day 21. Group: test group. Dose level: 0.5 ml. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: one animal with piloerection and hypoactivity.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5% w/w
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.5% w/w. No with. + reactions: 8.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5% w/w
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.5% w/w. No with. + reactions: 8.0. Total no. in groups: 10.0.

Any other information on results incl. tables

PRELIMINARY STUDY
Administration by intradermal route triggered a slight irritation at every dosage (25%, 50% and 75% w/w).

In contrast, administration by cutaneous route at the highest dosage (100% w/w) did not generate any erythema or oedema.


MAIN STUDY
Five females of the treated group were found dead on day 2, following intradermal injections. Hypoactivity and piloerection were noted between day 5 and day 21 in another animal. These mortalities and clinical signs were attributed to the test substance. No clinical signs and no deaths were noted in the remaining animals.
No cutaneous reactions were observed after the challenge application. The sensitivity of the guinea-pigs was satisfactory since
50% of the animals showed a positive reaction with DNCB.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to the maximization method of Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of the test substance METHYL UNDECYLENATE were observed in guinea-pigs.

Classification: not sensitizing
Executive summary:

The objective of this study, performed according to the maximization method of Magnusson and Kligman, was to evaluate the potential of the test substance METHYL UNDECYLENATE to induce delayed contact hypersensitivity in guinea-pigs. The results of the study are of value in predicting the contact sensitization potential of the test material in Man. The study was conducted in compliance with OECD guideline No. 406.

According to the maximization method of Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of the test substance METHYL UNDECYLENATE were observed in guinea-pigs. Five females of the treated group were found dead on day 2, following intradermal injections. Hypoactivity and piloerection were noted between day 5 and day 21 in another animal. These mortalities and clinical signs were attributed to the test substance. No clinical signs and no deaths were noted in the remaining animals. The body weight gain of the remaining animals was normal when compared to that of the control animals.

The relatively high number of death cases was due to systemic rather than due to hypersensitivity effects, as can be seen from the zero readings in all other test animals over the whole test duration. Fruthermore, even under the worst case assumption that the 5 out of 20 death cases were in some way hypersensitivity related, this still would not fulfil the condition for a positive Magnusson and Kligman test of positive reaction in at least 30% of the treated rabbits.

Therefore, the classification of test item METHYL UNDECYLENATE as to its skin sensitising properties would be "not sensitising".

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