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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The non-LLNA test (GPMT) was performed quite some time before the Local Lymph Node Assay was developed and evaluated, and a test guideline for the LLNA method was available. The results of the presentl GPMT can be used to assess the skin sensitisation potential of the registration substance.

Test material

Constituent 1
Reference substance name:
Creosote
EC Number:
232-287-5
EC Name:
Creosote
Cas Number:
8001-58-9
Molecular formula:
not applicable
IUPAC Name:
Creosote
Test material form:
liquid
Details on test material:
- Test material quality: Creosote Type WEI B (Grade B)
- Substance type: organic
- Analytical purity: not applicable (UVCB substance, distilled coal tar, complex hydrocarbon mixture)
- Impurities (identity and concentrations): not applicable
Specific details on test material used for the study:
- Name of test material (as cited in study report): Creosote SNCF
- Type of test material: Creosote Type WEI B (Grade B)
- Analytical purity: not applicable (UVCB, distilled coal tar, complex hydrocarbon mixture)
- Impurities (identity and concentrations): not applicable
- Source and lot/batch No.of test material: SNCF, 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
Vehicle:
petrolatum
Concentration / amount:
10 %
Day(s)/duration:
day 0 of treatment
Route:
intradermal
Vehicle:
other: test substance in 25 % FA
Concentration / amount:
5 %
Day(s)/duration:
day 0 of treatment
Route:
epicutaneous, open
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 mL test substance
Day(s)/duration:
day 7 of treatment
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 mL test substance
Day(s)/duration:
day 21 of treatment
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: 1
- Day(s) of challenge: day 21
- Exposure period: 24 h
- Test groups: test substance 100 %
- Control group: petrolatum
- Site: posterior side
- Concentrations: undiluted
- Evaluation: 24 h and 48 h 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 "Any other information on results ..."

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100% (neat substance, on the right)
No. with + reactions:
17
Total no. in group:
19
Clinical observations:
erythema; average score 1.2
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100% (neat substance, on the right)
No. with + reactions:
6
Total no. in group:
19
Clinical observations:
slight erythema; average score 0.4
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0 (vehicle only, on the left)
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
erythema - average score 0.0
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0 (vehicle only, on the left)
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
erythema - average score 0.0
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema - average score 0.0
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
erythema - average score 0.0
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 and 0.5%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
distinct erythema - average score 2.6
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 and 0.5%
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
distinct erythema - average score 2.3

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 (≥ 1 and 3) at both 24 and 48h after treatment.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Remarks:
as well as EU criteria according to CLP regulation
Conclusions:
Under the conditions of the test, the test substance creosote SNCF, WEI-Type B showed a skin sensitising potential in guinea pigs. A high percentage of animals responded, but at a low-grade intensity.