1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

D&C Yellow Nos 10 & 11: delayed contact hypersensitivity in the guinea pig

Author:

Susan . A. Lamson, Betty .M. Kong and Salvatore .J, D. Salva

Year:

1982

Bibliographic source:

Contact dermatitis 1982:8 200-203

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Data is from Journal with permission

Principles of method if other than guideline:

An irritation profiling was performed to determine thresholds for irritation

GLP compliance:

not specified

Type of study:

other: Modified Buehler test

Justification for non-LLNA method:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

EC Number:

232-318-2

EC Name:

1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

Cas Number:

8003-22-3

Molecular formula:

C18H11NO2

IUPAC Name:

2-(quinolin-2-yl)-2,3-dihydro-1H-indene-1,3-dione

Test material form:

other: Solid

Details on test material:

- Name of test material (as cited in study report): D &C Yellow No 11, Solvent Yellow-33 K 7064 (kohnstamm) 2(2-quinolyl)-1,3-indandione
- Molecular formula (if other than submission substance): C18H11NO2
- Molecular weight (if other than submission substance): 273.29
- Substance type: Organic
- Physical state: Solid
- Purity: No data available
- Impurities (identity and concentrations): No data available

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 300-500g
- Housing: 5 per cage
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: No data

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Induction 2

Concentration / amount:

95% ethanol

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Challenge 2

Concentration / amount:

95% ethanol

No. of animals per dose:

Total animals-13

Details on study design:

RANGE FINDING TESTS: No data available

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (Once weekly for 3 consecutive weeks)
- Exposure period: 24hr
- Test groups: 13
- Control group: 13, Concurrent
- Site: Nuchal area
- Frequency of applications: Once weekly
- Duration: 3 consecutive weeks
- Concentrations: 50%

B. CHALLENGE EXPOSURE
- No. of exposures: No data available
- Day(s) of challenge: No data available
- Exposure period: 24hr
- Test groups: 13
- Control group: 13, Concurrent
- Site: No data available
- Concentrations: 1.0, 3.0, 10.0%
- Evaluation (hr after challenge): after 24 hrs rest period

OTHER: One-tailed Mann-Whitney U Statistic (α₌ 0.05) was used to test for statistically significant differences between the scores in the test and vehicle control groups.

Positive control substance(s):

not specified

Results and discussion

Positive control results:

All skin responses in control animals were of low order.

In vivo (non-LLNA)

Results

Reading:

other: Sensitizing

Hours after challenge:

24

Group:

test chemical

Dose level:

10.00%

No. with + reactions:

11

Total no. in group:

13

Clinical observations:

Mild erythema, usually confluent (barely perceptible)

Remarks on result:

other: Reading: other: Sensitizing. . Hours after challenge: 24.0. Group: test group. Dose level: 10.00%. No with. + reactions: 11.0. Total no. in groups: 13.0. Clinical observations: Mild erythema, usually confluent (barely perceptible).

Any other information on results incl. tables

Frequency of skin sensitization responses in the guinea pig.

Animals group	D & C Yellow
	1%	3%	10%
Test	4/13	6/13	11/13
Vehicle control	3/13	2/13	2/13

Applicant's summary and conclusion

Interpretation of results:

other: Weakly Sensitizing

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test compound D &C yellow no. 11 induced delayed type skin sensitization in guinea pig and is found to be a sensitizing to the skin of guinea pigs.

Executive summary:

Modified Buehler test was performed to study the sensitizing potential ofD &C yellow no. 11 to the skin of Guinea pigs.

The induction phase was accomplished with 24 hr occluded patch in nuchal area once weekly for three consecutive weeks following 2 week resting period. Pigs were initially challenged with dye used during the induction phase and then with the concentration of 1.0, 3.0 and 10%.Thereafter the patches were removed and the guinea pigs were rested for 24 hrs depilated with a chemical depilatory and evaluated and scored for erythema and edema.

D &C yellow no. 11 at a challenge concentration of 10% elicited delayed skin sensitization in 11 of 13 animals and hence is a weak sensitizer. Lower concentrations did not elicit statistically significant response.

According to the publication, the test material is a skin sensitizer.