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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:
June 18, 1979 to July 26, 1979
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:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Essentially according to E. V. Buehler, "Delayed Contact Hypersensitivity in the Guinea Pig", Arch. Dermat., 91 (1965), pp. 171-175.
Deviations:
yes
Remarks:
Number of animals < 20 and nine inducing applications instead of three according to the OECD 406.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Study is performed before introduction of the LLNA method as a sensitization study.

Test material

Constituent 1
Chemical structure
Reference substance name:
1-Propanaminium, 3-amino-N-(2-hydroxyethyl)-N,N-dimethyl-, N-mink-oil acyl derivs., chlorides
EC Number:
273-222-0
EC Name:
1-Propanaminium, 3-amino-N-(2-hydroxyethyl)-N,N-dimethyl-, N-mink-oil acyl derivs., chlorides
Cas Number:
68953-64-0
Molecular formula:
UVCB: CnHnN2 O2 (Cl)
IUPAC Name:
1-Propanaminium, 3-amino-N-(2-hydroxyethyl)-N,N-dimethyl-, N-mink-oil acyl derivs., chlorides
Details on test material:
Supplied by: Van Dyk & Company, Inc.
Received on: June 15, 1979
Identified as: Ceraphyl 65, Batch #6371

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Supplier: The animals were obtained through a suitably licensed breeding farm, and were carefully checked upon receipt and prior to test initiation for evidence of poor health.
Housing: They were housed in galvanized or stainless steel cages and were identified through individual markings as well as cage labels.
Diet: consisted of a growth and maintenance ration from a commercial producer
Water: ad libitum.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.5 mL of 25% test article
Day(s)/duration:
Applications were made 3 times weekly for 3 weeks
Adequacy of induction:
other: Prior to initiation of the induction phase of the experiment, the highest nonirritating concentration of the test article was determined. A dilution containing 25% of test article was used for the sensitization test.
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.5 mL of 25% test article
Day(s)/duration:
Two weeks after the ninth induction application
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
Skin irritation pre-test:
Prior to initiation of the induction phase of the experiment, the highest nonirritating concentration of the test article was determined. The animals were prepared by close-clipping the mid-dorsal area of the trunk with a small animal clipper equipped with a 1/4-0 (surgical) head. Decreasing concentrations of the test article, suspended or dissolved in an appropriate, non-irritating vehicle, were applied to guinea pigs under occluded patch for 16 hours. At the end of 16 hours, the occlusive wrap was removed and the test site scored then and at 24- hours for erythema and edema. (Refer to the scoring scale appended.) The highest concentration tested which produced no irritation was chosen for the induction phase.
For induction:
0.5 milliliter of the test article applied to the test site of each animal under occluded patch.
After a minimum of 6 hours, the patch and remaining test article were removed and the test site scored for erythema and edema.
Applications were made 3 times weekly for 3 weeks.
Challenge:
Two weeks after the ninth induction application, a challenge application was made to the original test site and a virgin site, to test for both local and systemic effects.
The challenge sites were scored after 6 hours and again at 24-hours.
Gross necropsy
Animals which survived the full term of the study, as well as any non-survivors, were subjected to complete gross necropsy, with all findings noted. Initial and terminal bodyweights were recorded.
Since a non-irritating concentration of the sensitizer was used, any reaction at challenge was considered positive, the severity of which was proportional to the score obtained.
Challenge controls:
Dorsal Challenge for topical effects
Ventral Challenge for systemic effects
Positive control substance(s):
not required

Results and discussion

Positive control results:
Not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Dorsal Challenge for topical effects
Hours after challenge:
6
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
No gross changes observed
Key result
Reading:
other: Dorsal Challenge for topical effects
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
No gross changes observed
Reading:
other: Ventral Challenge for systemic effects
Hours after challenge:
6
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
No gross changes observed
Key result
Reading:
other: Ventral Challenge for systemic effects
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
No gross changes observed
Group:
negative control
Remarks on result:
not measured/tested
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Phase Induction, Observations: Slight to moderate irritation persisting through last dose.
Phase Challenge, Observations: No positive reactions observed.
This test article is not a potential sensitizer to guinea pigs under conditions of this test.
Executive summary:

Twelve Hartley-strain guinea pigs, male, 286 - 338 grams, acclimated for 7 days prior to test initiation each received 9 topical, occluded applications of a non-irritating concentration of the test article during the induction period of 3 weeks. Two (2) weeks following the last induction application, the animals received 2 topical applications of the test article--one on the original test site, and another on a virgm test s1te. 0 servations of erythema, edema, and other effects were recorded at the end of each daily 6 hour application period, and 24 hours following the challenge applications. The test article was used in 25% gravimetric aqueous concentration. This test article is not a potential sensitizer to guinea pigs under conditions of this test.

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