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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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline available
Version / remarks:
Method of Magnusson and Kligman
Principles of method if other than guideline:
Mehtod of Magnusson and Kligman "Allergic Contact Dermatitis in Guinea Pigs", Ed. Ch.C. Thomas, Springfield, Illinois, USA (1970).
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This in vivo GPMT fulfills the skin sensitisation endpoint, follows a well reviewed and accepted guidance at the time, is well documented and the results are very clearly negative.

Test material

Constituent 1
Chemical structure
Reference substance name:
11-oxahexadecan-16-olide
EC Number:
222-225-5
EC Name:
11-oxahexadecan-16-olide
Cas Number:
3391-83-1
Molecular formula:
C15H28O3
IUPAC Name:
11-oxahexadecan-16-olide
Test material form:
liquid
Specific details on test material used for the study:
Musk R1, T 02437, No. 148983.

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino SPF
Remarks:
Acceptable strain of guinea pig used routinely at the time of the study.
Sex:
male
Details on test animals and environmental conditions:
Acclimatisation: 2 days.
Room temperature: 23-25'C.
Relative humidity: 40-70%.
Day/Light cycle: 12 hours each.

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
polyethylene glycol
Concentration / amount:
2% Musk R1 as this was the lowest irritating dose level.
Day(s)/duration:
1 day, 6 injections
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
10%
Day(s)/duration:
48 hours
Adequacy of challenge:
not specified
No. of animals per dose:
Control: 5 animals.
Musk R1: 10 animals.
Details on study design:
Intradermal injections of the test substance were given both after mixing with Freunds adjuvant and also after diluting with propylene glycol (PG),. An area of 4x6 cm of the shoulder region was shaved with electric clippers. Then within a few minutes the 6 intradermal injections were given in an area of 2x4 cm in 2 rows of 3.

Induction: Control animals:
1). 2 injections with Adjuvant.
2). 2 injections with PG.
3). 2 injections with PG + Adjuvant (1:1).

Induction: Test Substance animals:
1). 2 injections of 0.05 ml Freund's Adjuvant.
2). 2 injections of 0.05 ml of a 2% Musk R1 dilution in PG.
3). 2 injections of 0.05 ml of a 2% Musk R1 dilution in PG and Adjuvant (1:1).

One week later:
The same area was shaved again. A patch of 2x4 cm Whatman 3mm filter paper was spread with a 10% dilution of Musk R1 in vaseline and then placed on the shaved skin covered by paraplast which was kept in place by adhesive bandage. This in turn was firmly secured bu self sticking tape and left in place for 48 hours.

Challenge:
The animals were challenged at day 14 after the topical induction on the right flank of which an area of 5x5 cm was shaved. For this treatment Musk R1 was mixed with vaseline. A concentration of 10% (w/w), which proved to be non-irritationg in a preliminary test, was used for the challenge.
A small amount of the 10% mixture was applied to the shaved area of each animal and gently massaged in with a glass rode for 30 seconds. The material was applied to an area of 2x2 cm and was covered by a patch of 2x2 cm Whatman 3mm filter paper and paraplast, kept in place by adhesive bandage and firmly secured by self sticking tape. At the same time the the challenge treatment was applied to the 5 control animals.
Skin readings were made 24 hours after the challenge treatment in both control and test animals.
Skin reactions were judged by the method of Draize, as decribed in J. Pharmacol. 82 (1944) 377-390.
Challenge controls:
At the same time the the challenge treatment was applied to the 5 control animals.
Positive control substance(s):
no
Remarks:
No required for this assessment as not ethitically appropriate.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
Induction phase: No Clinical observations. Challenge phase: No Clinical observations.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Induction phase: Slight edema and abscesses. Challenge phase: No Clinical observations.
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The 10% dilution of Musk R1 in vaseline induced neither erythema nor edema upon topical application in the induction phase of the study.
The challenge dose of 10% provoked no positive reactions in the 10 test substance animals. At the same time none of the 5 control animals reacted positively either.
Executive summary:

On the basic of the results obtained , the test substance Musk R1 exhibited no sensitisation properties according to the classification of Magnusson and Kligman (1970).

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