Pitch, coal tar, high-temp.

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study based on scientific principles, reproducible test method

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1963

Reference 2

Reference Type:

review article or handbook

Title:

Selected non-heterocyclic polycyclic aromatic hydrocarbons. Environmental Health Criteria 202

Author:

WHO

Year:

1998

Bibliographic source:

International Programme on Chemical Safety (IPCS), World Health Organization, Geneva, Switzerland

Reference 3

Reference Type:

review article or handbook

Title:

Toxicological Profile for Polycyclic Aromatic Hydrocarbons

Author:

ATSDR

Year:

1995

Bibliographic source:

US Department of Health & Human Services, Agency for Toxic Substances and Disease Registry, August 1995, 1-487

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Delayed hypersensitivity/contact sensitisation: Intradermal injection of the agents into the foot pad for induction in the presence of Freund´s adjuvant, followed by topical/epidermal challenge
(method according to: Gell PG and Benacerraf B J. Exp. Med. 113, 571 (1961)

GLP compliance:

no

Type of study:

intracutaneous test

Test material

Test material information

Constituent 1

Reference substance name:

Benzo[def]chrysene

EC Number:

200-028-5

EC Name:

Benzo[def]chrysene

Cas Number:

50-32-8

Molecular formula:

C20H12

IUPAC Name:

benzo[pqr]tetraphene

Constituent 2

Reference substance name:

benzo(a)pyrene / benzo(def)chrysene

IUPAC Name:

benzo(a)pyrene / benzo(def)chrysene

Details on test material:

- Name of test material (as cited in study report): 3,4-benzpyrene (BP)
- Molecular formula (if other than submission substance): C20H12
- Molecular weight (if other than submission substance): 252.3
- Substance type: organic
- Physical state: solid
- Analytical purity: "highly purified" (acc. to report)
- Impurities (identity and concentrations):

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

other: intradermal into each front food pad, single dose 125 µg each (total 250 µg)

Vehicle:

other: acetone-olive oil mixture (no further data)

Induction 2

Concentration / amount:

Challenge: 0.001, 0.01, 0.1, and 1 %

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: acetone-olive oil mixture (no further data)

Challenge 2

Concentration / amount:

Challenge: 0.001, 0.01, 0.1, and 1 %

No. of animals per dose:

6, 16, and 10 were used for 3-methylcholanthrene (MC), BaP and 9,10-dimethyl-1,2-benzanthracene (DMBA), respectively

Details on study design:

RANGE FINDING TESTS: no data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 i.d.
- Exposure period: 2 - 3 weeks
- Test groups: 4
- Control group: 1
- Site: each foot pad
- Frequency of applications: 1x
- Concentrations: 250 µg (125 µg/0.1 mL)
- Auxiliary agent: emulsion in complete Freund´s adjuvant with saline


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 - 3 weeks after induction
- Exposure period: 24 h
- Test groups: 4
- Control group: 1
- Site: ventral or dorsal shaved skin
- Concentrations: 0.001, 0.01, 0.1,and 1 % (one drop each applied)
- Evaluation (hr after challenge): 24


OTHER:
- Scoring system
according to Gell PG and Benacerraf B J. Exp. Med. 113, 571 (1961): from +++ to 0

Challenge controls:

PAH known to be contact sensitisers in this test system: MC and DMBA

Positive control substance(s):

yes

Remarks:

MC and DMBA

Results and discussion

Positive control results:

MC +++ (>= 0.1 %); DMBA +++ (1 %).
Dose-related intensity of the responses

In vivo (non-LLNA)

Results

Results 1

Hours after challenge:

24

Group:

negative control

Dose level:

0.001 - 1 %

Clinical observations:

reponse - to +- (slight erythema)

Remarks on result:

other: . Hours after challenge: 24.0. Group: negative control. Dose level: 0.001 - 1 %. Clinical observations: reponse - to +- (slight erythema).

Results 2

Hours after challenge:

24

Group:

test chemical

Dose level:

0.001%

Clinical observations:

contact reactivity with score +

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 0.001%. Clinical observations: contact reactivity with score +.

Results 3

Hours after challenge:

24

Group:

test chemical

Dose level:

0.01%

Clinical observations:

contact reactivity with score ++

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 0.01%. Clinical observations: contact reactivity with score ++.

Results 4

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

Clinical observations:

contact reactivity with score +++

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 0.1%. Clinical observations: contact reactivity with score +++.

Results 5

Hours after challenge:

24

Group:

test chemical

Dose level:

1 %

Clinical observations:

contact reactivity with score +++

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 1 %. Clinical observations: contact reactivity with score +++.

Any other information on results incl. tables

There was a dose-related increase in the intensity of the delayed contact reactivity. There was also cross-reactivity with MC and DMBA as challenging agent and BaP with previous inducer. The intensity of the response was dose-related but primarily expressed at the higher challenge doses, i.e. weaker than with BaP as challenger.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information