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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed journals

Data source

Reference
Reference Type:
publication
Title:
The sensitizing capacity of coumarins (III)
Author:
B.M. HAUSEN AND M. Berger
Year:
1989
Bibliographic source:
Contact Dermatitis,1989, 21: 141-147

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Modified FCA method and Guinea pig maximization test
Principles of method if other than guideline:
Modified FCA method and Guinea pig maximization test was performed to evaluate the dermal sensitization potential of the test chemical
GLP compliance:
not specified
Type of study:
other: Modified FCA method and Guinea pig maximization test
Justification for non-LLNA method:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): 7-DIETHYLAMINO-4-METHYLCOUMARIN
- Molecular formula: C14H17NO2
- Molecular weight : 231.2933 g/mol
- Substance type:Organic
- Physical state:Solid

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbrigjht white strain
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: No Data available
- Weight at study initiation:280-350 g
- Housing: animals were kept 3 to a cage
- Diet (e.g. ad libitum):altromin ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: No Data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22-24⁰C
- Humidity (%):50-55%
- Air changes (per hr): No Data available
- Photoperiod (hrs dark / hrs light): Under artificial illumination for 10 hours a day

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: FCA and saline
Concentration / amount:
15 mg
Day(s)/duration:
5th and 9th day
Adequacy of induction:
not specified
Challenge
No.:
#10
Route:
epicutaneous, open
Vehicle:
other: Acetone
Concentration / amount:
0.05ml
Adequacy of challenge:
other: subirritent concentration.
No. of animals per dose:
Induction route-10
Challenge route-10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 8
- Exposure period:9 days
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs
- Site: Intradermal induction -Intraderma injection of 6x0.10-0.15 ml of emulsion were applied.The emulsion was applied in a semicircular arc on clipped and shaved shoulder area (4Х6 cm) from left to right.
- Frequency of applications: repeated on 5th and 9th days
- Duration: 9 days
- Concentrations: 15 mg in 4 ml FCA

B. CHALLENGE EXPOSURE
- No. of exposures: multiple times
- Day(s) of challenge: 11 days after induction, animals were challenged.
- Exposure period:5 mins
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs
- Site: clipped and shaved skin of the right flank of treated animals.
- Concentrations:0.05ml
- Evaluation (hr after challenge): after 24, 48 and 72 hr.
Challenge controls:
No data available.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Results
Key result
Reading:
other: Mean
Hours after challenge:
72
Group:
test group
Dose level:
0.05ml
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Non sensitizer
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Sensitizer

Challenged with

Concentration

24 hour

48

hour

72

hour

24 hour

48

hour

72

hour

 

 

 

+++

++

+

(+)

0

-

-

-

-

10

+++

++

+

(+)

0

-

-

-

-

10

+++

++

+

(+)

0

-

-

-

-

10

0

0

0

The mean response was computed as the quotient of the sum of the observed reactions and the number of the treated animals.

Applicant's summary and conclusion

Interpretation of results:
other: not sensitising
Conclusions:
No sensitization effects were observed after 72 hours post challenge exposure. Hence, the test chemical can be considered as non -sensitizing to the female guinea pigs.
Executive summary:

Modified FCA method and Guinea pig maximization test was performed to evaluate the dermal sensitization potential of the test chemical. 20 female Pirbright White guinea pigs were used for the study.

.In the induction phase, the test compound was dissolved in FCA, 15 mg in 4 ml physiological saline and an emulsion was prepared by mixing the material by mean of a 5ml syringe, until emulsification was completed. The intradermal injections of 6 X 0.10-0.15 ml of this emulsion was applied in a semi circle arc on clipped and shaved shoulder from left to right in such a way that whole quantity of emulsion was used up for 10 animals. This procedure was repeated on 5thand 9thday, leaving a gap of 2-3 cm between the rows of injection. After induction phase of 11 days, animals were challenged by applying 0.05ml of test chemical in a sub irritant concentration, with further dilution to the clipped and shaved skin of the right flank of the treated animals, allowing 5 mins for drying. Control animals were also used. Mean Observations were made after 24, 48 and 72 hours.

No sensitization effects were observed after 72 hours post challenge exposure. Hence, the test chemical can be considered as non -sensitizing to the female guinea pigs.