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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
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


Route:
intradermal and epicutaneous
Vehicle:
petrolatum
Concentration / amount:
see below "Any other information on materials..."
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)
Positive control results:
see below "Remarks on results..."
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.

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.
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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No data on sensitisation is available for the substance distillates (coal tar), heavy oils (anthracene oil high (> 50 ppm) BaP, AOH) itself. Data obtained originate from the closely related tar oil creosote and from the minor constituent benzo[a]pyrene (BaP).

Due to the similar production process (fractionated distillation of coal tar using overlapping conditions), composition of both tar substances correspond to each other. Major components are mid-range PAH for both substances (3- and 4-ring PAH) with some additional 2-ring PAH in creosote but not in AOH.

3- and 4-ring PAH are considered to contribute predominantly to the sensitising potency of creosote. 2-ring PAH will not have an additional substantial effect. But in case they have, using creosote data to represent the sensitising potency of AOH will result in overestimation of the sensitising effect of AOH as worst case. Thus, use of creosote as supporting substance for characterisation of the sensitising potential of AOH is justified.

Creosote was found to be skin sensitising in a guinea pig maximisation test (Clouzeau J, 1993d). Based on this result, AOH is characterised as sensitising. Furthermore, BaP as constituent of AOH showed itself a strong sensitising effect in a delayed hypersensitivity/contact sensitisation test (Old et al.1963) after intradermal induction in the foot pad of guinea pigs. Based on both results, AOH is identified as skin sensitiser.


Migrated from Short description of key information:
AOH is characterised as skin sensitising based on experimental results for the closely structure-related tar oil creosote. Sensitising properties also result from its constituent benzo[a]pyrene present in AOH at a concentration up to 1.5 % exceeding the generic concentration limit of ≥ 1.0 % that requires classification of the mixture the same way as the constituent.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

For respiratory sensitisation, no experimental data has been located. Due to the low vapour pressure of AOH at ambient temperature (0.6 Pa, see Chapter 1.3), respiratory effects are not expected. From occupational experience, there has been no evidence of respiratory sensitisation in exposed workers.


Migrated from Short description of key information:
No experimental data on respiratory sensitisation has been located. Based on occupational experience, there is no evidence of respiratory sensitisation at ambient temperatures (low vapour pressure of the substance).

Justification for classification or non-classification

Skin sensitising potential was demonstrated for distillates (coal tar), heavy oils (AOH) in a studies with the supporting substance creosote and in a study with the AOH constituent benzo[a]pyrene (BaP).

BaP is classified as skin sensitising Cat. 1 according to Annex VI, Table 3.1 of Regulation (EC) No 1272/2008. According to table 3.5.2 of this regulation, the generic concentration limit of a constituent classified as Skin Sens. 1ina mixture that triggers classification of the mixture the same way as the constituent is≥ 1.0 %.Due to this provision, AOH is to be classified (self-classification) as skin sensitising Cat. 1.