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Toxicological information

Skin sensitisation

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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: 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 - IPCS Environmental Health Criteria 202 (§)
Author:
WHO
Year:
1998
Bibliographic source:
International Programme on Chemical Safety (IPCS), WHO - 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

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
Justification for non-LLNA method:
LLNA test method not available at time of the study

Test material

Constituent 1
Chemical structure
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
Test material form:
solid
Details on test material:
- Substance type: organic
Phys.-chem. properties (data from EU 2008: Coal-Tar Pitch, high temperature - Risk Assessment. European Union Risk Assessment Report, The Netherlands, and WHO 1998: EHC 202)
- Vapour pressure: 7.3E-7 Pa (at 25 °C)
- Water solubility: in freshwater, approx. 1.5 - 3.8 µg/L (20 - 25 °C);
- Henry's law constant: 0.034 Pa*m³/mol (at 20 °C)
- log Pow: = 6.13 - 6.5
- pKa: not applicable
- Stability in water: limited due to photolytic decomposition and evaporation
- Stability in light: instable in the presence of UV
- pH dependance on stability: not applicable
Specific details on test material used for the study:
- Name of test material (as cited in study report): 3,4-benzpyrene (BP)
- Analytical purity: "highly purified" (acc. to report)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
other: emulsion in complete Freund´s adjuvant with saline
Concentration / amount:
125 µg into each front foot pad, total 250 µg
Day(s)/duration:
exposure period 2 - 3 wks
Adequacy of induction:
not specified
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: acetone-olive oil mixture (not further specified)
Concentration / amount:
0.001 %
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: acetone-olive oil mixture (not further specified)
Concentration / amount:
0.01 %
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No.:
#3
Route:
epicutaneous, open
Vehicle:
other: acetone-olive oil mixture (not further specified)
Concentration / amount:
0.1 %
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No.:
#4
Route:
epicutaneous, open
Vehicle:
other: acetone-olive oil mixture (not further specified)
Concentration / amount:
1 %
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
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 into each front foot pad)
- 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:
3- methylcolanthrene (MC) and 9,1-dimethyl-1,2-benzanthracene (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
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.001%
No. with + reactions:
16
Total no. in group:
16
Clinical observations:
contact reactivity with score +
Remarks on result:
positive indication of skin sensitisation
Remarks:
score + indicates the onset of a sensitising effect
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.01%
No. with + reactions:
16
Total no. in group:
16
Clinical observations:
contact reactivity with score ++
Remarks on result:
positive indication of skin sensitisation
Remarks:
score ++ shows a moderate sensitising response
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
16
Total no. in group:
16
Clinical observations:
contact reactivity with score +++
Remarks on result:
positive indication of skin sensitisation
Remarks:
score +++ demonstrates a clear sensitising response
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1 %
No. with + reactions:
16
Total no. in group:
16
Clinical observations:
contact reactivity with score +++
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
solvent without test substance
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
reponse - to +- (negative to slight erythema)
Remarks on result:
no indication of skin sensitisation
Remarks:
negative response on challenge
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 %
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
Score ++
Remarks on result:
positive indication of skin sensitisation
Remarks:
score ++ shows a moderate sensitising response

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:
Category 1 (skin sensitising) based on GHS criteria
Remarks:
dose related intensity of the response with regard to the test substance concentration during challenge