2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]-1,3-dimethyl-1H-benzimidazolium chloride

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

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

Guideline:

other: As given below

Principles of method if other than guideline:

Skin sensitization test of 7-Diethylamino-4-methylcoumarin (CAS No: 91-44-1) was conducted on guinea pigs by guinea pig maximization test to determine its sensitization potential.

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

Test material information

Constituent 1

Reference substance name:

7-(diethylamino)-4-methyl-2-benzopyrone

EC Number:

202-068-9

EC Name:

7-(diethylamino)-4-methyl-2-benzopyrone

Cas Number:

91-44-1

Molecular formula:

C14H17NO2

IUPAC Name:

7-(diethylamino)-4-methyl-2H-chromen-2-one

Test material form:

other: off white crystalline 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: off white crystalline solid

Specific details on test material used for the study:

- 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: off white crystalline solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: albino Pirbright White

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 in 4 ml FCA, then 4ml of physiological saline and emulsion was prepared by mixing them with the help of a 5ml syringe. 6*0.10-0.15 ml of the prepared emulsion was given as an intradermal injection

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

Day(s)/duration:

5 minutes(multiple times)

Adequacy of challenge:

other: subirritant 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, then 4ml of physiological saline and emulsion was prepared by mixing them with the help of a 5ml syringe. 6*0.10-0.15 ml of the prepared emulsion was given as an intradermal injection

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

Study design: in vivo (LLNA)

Statistics:

Mean response was computed as the quotient of the sum of the observe reaction and the number of the trated animals

Results and discussion

In vivo (non-LLNA)

Results

Reading:

other: Mean

Hours after challenge:

72

Group:

test chemical

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

Table: Results of the sensitization experiments

Sensitizer	Challenged with		Concentration	24 hours					48 hours					72 hours					24 hours	48 hours	72 hours
				+++	++	+	(+)	0	+++	++	+	(+)	0	+++	++	+	(+)	0
Coumarin 1	Coumarin 1		10%	-	-	-	-	10	-	-	-	-	10	-	-	-	-	10	0.0	0.0	0.0

 

Applicant's summary and conclusion

Interpretation of results:

other: not sensitising

Conclusions:

No allergic or irritant effects of 7 -Diethylamino-4-methylcoumarin (CAS No: 91-44-1) were observed throughout the study. Hence, -Diethylamino-4-methylcoumarin (CAS No: 91-44-1) can be considered to be not sensitizing to guinea pig skin.

Executive summary:

Skin sensitization test of 7-Diethylamino-4-methylcoumarin (CAS No: 91-44-1) was conducted on guinea pigs by guinea pig maximization test to determine its sensitization potential.The experiment was performed by a method involving modifications of the FCA-method and Guinea pig maximization test. 10 albino 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. Then 4 ml of physiological saline was added and an emulsion was prepared by mixing the material by mean of a 5ml syringe, until emulsification was completed. 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 5^thand 9^thday. , 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 subirritant 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. The mean response was computed as the quotient of the sum of the observed reactions and the number of the treated animals.

 

 No allergic or irritant effects of 7-Diethylamino-4-methylcoumarin (CAS No: 91-44-1) were observed throughout the study. Hence, -Diethylamino-4-methylcoumarin (CAS No: 91-44-1) can be considered to be not sensitizing to guinea pig skin.