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Toxicological information

Skin sensitisation

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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Creosote SNCF
- Creosote Type WEI B (Grade B)
- Molecular formula (if other than submission substance): not applicable
- Molecular weight (if other than submission substance): not applicable
- Substance type: organic
- Physical state: liquid
- Analytical purity: not applicable (UVCB, distilled coal tar, complex hydrocarbon mixture.)
- Impurities (identity and concentrations): not applicable
- Composition of test material, percentage of components: see below "Any other information on test materials...."
- Batch No. 4460 A 93
- Storage condition of test material: Stable at room temperature under exclusion of UV light

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre d´Elevage Lebeau, 78950 Gambais, France
- Age at study initiation: no data
- Weight at study initiation: Males: 395 ±22 g, females: 407 ±24 g
- Housing: polycarbonate cages, 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-3
- Humidity (%): 50 +-20
- Photoperiod (hrs dark / hrs light): 12 / 12


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
see below "Any other information on materials..."
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
see below "Any other information on materials..."
No. of animals per dose:
10 animals (5m/5f) untreated control; 20 animals (10m/10f) test article
Details on study design:
RANGE FINDING TESTS: yes


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Test groups: see below "any other information on materials..."
- Site: anterior side
- Duration: 24 d
- Concentrations: 1st induction: 10 % in petrolatum; 2nd induction: undiluted test article


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: Day 21
- Exposure period: 24 h
- Test groups: test substance 100 %
- Control group: petrolatum
- Site: posterior side
- Concentrations: undiluted
- Evaluation: 24h + 48h after termination of challenge exposure

Positive control substance(s):
yes
Remarks:
5 female animals positive control (1-Chloro-2,4-dinitrobenzene = DNCB) (not concurrent)

Results and discussion

Positive control results:
see below "Remarks on results..."

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 %
No. with + reactions:
17
Total no. in group:
19
Clinical observations:
average score: 1.2
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 17.0. Total no. in groups: 19.0. Clinical observations: average score: 1.2.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
6
Total no. in group:
19
Clinical observations:
average score 0.4
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 6.0. Total no. in groups: 19.0. Clinical observations: average score 0.4.

Any other information on results incl. tables

Guinea pig maximisation test with the test substance Creosote SNCF:

Result of skin sensitisation test (Challenge)

Number of animals with signs of allergic reactions /
number of animals in group

Negative control

Test group

Positive control (not concurrent)

scored after 24 h

0/10
average score 0.0

17/19
average score 1.2

5/5
average score 2.6

scored after 48 h

0/10
average score 0.0

6/19
average score 0.4

5/5
average score 2.3

*Scoring system: Draize grading

0 = no reaction; 1 = slight erythema; 2 = well visible erythema; 3 = moderate erythema; 4 = strong erythema

A spontaneous death occurred in one female animal on day 9 with no relation to the treatment.After challenge with the test article, there was a brownish discolouration at the site of application and, additionally, dryness of the skin after 48 h p.a..

Discolouration but no dryness is also reported for the not-induced control group.

The induced animals showed slight to well defined erythema (definition see table below):

·        24 h after challenge exposure: 5/19 score 2, 12/19 score 1 and 2/19 score 0   and

·        48 h after challenge exposure: 1/19 score 2, 5/19 score 1, and 13/19 score 0.

All animals treated with DNCB (positive controls) exhibited positive dose-related scores (≥1and ≥3) at both 24 and 48 h after treatment.

Applicant's summary and conclusion

Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of the test, the test substance, Creosote SNF, showed a skin sensitising potential in guinea pigs. A high percentage of animals responded, but at a low-grade intensity.