1H,3H-Naphtho[1,8-cd]pyran-6,7-dicarboxylic acid, 1,3-dioxo-

Skin sensitisation

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:

other: Test performed prior to the implementation of the current acknowledged OECD testing and GLP guidelines . The test was conducted according to the method of Magnusson and Kligman.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Magnusson & Kligman

GLP compliance:

no

Remarks:

pre-guideline study

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dioxo-3-oxatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene-8,10-dicarboxylic acid

EC Number:

619-817-4

Cas Number:

52671-72-4

Molecular formula:

C14H6O7

IUPAC Name:

2,4-dioxo-3-oxatricyclo[7.3.1.0⁵,¹³]trideca-1(13),5,7,9,11-pentaene-8,10-dicarboxylic acid

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Pirbright-White

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
-Strain specifics: Hoe: DHPK (SPFLac)
- Source: Hoechst AG, breeding colony
- Weight at study initiation: mean 332 g (range: 240-580 g)

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: Freund's Adjuvant

Induction 2

Concentration / amount:

INDUCTION EXPOSURE: 500 mg test item was mixed with 10 mL Freund's Adjuvant
0.05 mL were injected respectively

CHALLENGE EXPOSURE: 0.5 % in 2 % starch mucilage (non-irritant concentration determined in pilot test and preliminary patch test)
0.5 mL were administered via patch (occlusive) respectively

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: Freund's Adjuvant

Challenge 2

Concentration / amount:

INDUCTION EXPOSURE: 500 mg test item was mixed with 10 mL Freund's Adjuvant
0.05 mL were injected respectively

CHALLENGE EXPOSURE: 0.5 % in 2 % starch mucilage (non-irritant concentration determined in pilot test and preliminary patch test)
0.5 mL were administered via patch (occlusive) respectively

No. of animals per dose:

PILOT TEST (for determination of a primary non-irritant concentration range):
6 concentrations / 1 animal per concentration

PRELIMINARY PATCH TEST (for determination of a primary non-irritant concentration for challenge exposure):
5 concentrations / 1 animal per concentration

MAIN STUDY:
1 concentration / 15 animals per concentration

Details on study design:

RANGE FINDING TESTS:

PILOT TEST for determination of a primary non-irritant concentration range:

test item concentrations in 2 % starch mucilage: 40 %, 20 %, 10 %, 5 %, 1 %, 0.1 %
0.5 mL were administered to the shaved flank respectively

PRELIMINARY PATCH TEST determination of a primary non-irritant concentration for challenge exposure:

test item concentrations in 2 % starch mucilage: 8 %, 5 %, 3 %, 1 %, 0.5 %
0.5 mL were administered via patch respectively


MAIN STUDY:

A. INDUCTION EXPOSURE
- No. of exposures: 10 intradermal injections within 14 days
- Exposure period: 15 days without treament
- Site: shaved flank measuring about 30 cm^2 for intradermal injections
- Concentrations: see above

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28 of study
- Site: untreated flank
- Concentrations: primary non irritent concentration of 0.5% according to the PRELIMINARY PATCH TEST
- Evaluation (hr after challenge): 24 h, 48 h and 72 h

Challenge controls:

no controls reported

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

other:

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 %

No. with + reactions:

15

Total no. in group:

15

Clinical observations:

distinct erythema

Remarks on result:

other: Reading: other:. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 %. No with. + reactions: 15.0. Total no. in groups: 15.0. Clinical observations: distinct erythema.

Results 2

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 %

No. with + reactions:

13

Total no. in group:

15

Clinical observations:

slight or distinct erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 %. No with. + reactions: 13.0. Total no. in groups: 15.0. Clinical observations: slight or distinct erythema.

Results 3

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

0.5 %

No. with + reactions:

6

Total no. in group:

15

Clinical observations:

slight erythema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.5 %. No with. + reactions: 6.0. Total no. in groups: 15.0. Clinical observations: slight erythema.

Any other information on results incl. tables

During the induction exposure intradermal injections with a mixture of 500 mg test substance + 10 ml Freund's adjuvant caused severe erythema at the entire flanks as well as injection site necrosis in all animals within 8 days. Lesions partly healed, but erythema persisted until the end of the subsequent 15 days rest period.

For the challenge exposure 0.5 % test substance in 2 % starch mucilage were administered via patch/occlusive bandage to the untreated flanks respectively. All animals showed distinct erythema after 24 h. 48 h p.a. slight or distinct erythema were observed in 13 animals, 72 h p.a. slight erythema were still present in 6 animals.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

In a guinea pig maximisation test according to the method of Magnusson and Kligman, the test item caused distinct skin reactions in all 15 animals of the treatment group after challenge exposures. Based on the results of this study the test item showed some evidence for sensitising properties although the reliablity is restricted by missing positive and negative controls.

Executive summary:

Testing for sensitizing properties of the test item was performed in 15 male guinea pigs according to the method of Magnusson & Kligman. Intradermal induction was performed using 5 % test item preparation in Freund's adjuvant. Within 8 days of the induction exposure severe erythema and injection sites necroses were recorded in all animals. After a rest period of 15 days challenge treatment was carried out with 0.5 % test item in 2 % starch mucilage. The challenge treatment caused distinct erythema in all 15 animals of the treatment group after 24 h. Slight erythema were still present in 6 animals 72 h p.a.

Therefore the test substance was considered to be a skin sensitiser, category 1 according to regulation (EC) No 1272/2008.