Registration Dossier

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

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1963
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 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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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)

Inductionopen allclose all
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)
Concentration / amount:
Challenge: 0.001, 0.01, 0.1, and 1 %
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: acetone-olive oil mixture (no further data)
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)

Resultsopen allclose all
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).
Hours after challenge:
24
Group:
test group
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 +.
Hours after challenge:
24
Group:
test group
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 ++.
Hours after challenge:
24
Group:
test group
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 +++.
Hours after challenge:
24
Group:
test group
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