Registration Dossier

Administrative data

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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant, near guideline study, available as unpublished report, restrictions in study design but otherwise adequate for assessment.
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OTS 798.4100 (Skin Sensitisation)
Deviations:
yes
Remarks:
only 10 per group
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Camm Research, Wayne, New Jersey, USA
- Age at study initiation: Young adults
- Weight at study initiation: 300-500 g
- Housing: Individually in stainless steel, wire mesh bottom cages
- Diet: Agway guinea pig feed ad libitum
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 64-79°F (~17.8 -26°C)
- Humidity: 40-70%
- Air changes: at least 10 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 4 April 1990 To: 4 May 1990
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: Undiluted for induction phases 1 and 2 and as a 1:2 v/v dilution in mineral oil for induction 3.
Challenge: 1:4 v/v dilution in mineral oil
Route:
epicutaneous, occlusive
Vehicle:
other: mineral oil
Concentration / amount:
Induction: Undiluted for induction phases 1 and 2 and as a 1:2 v/v dilution in mineral oil for induction 3.
Challenge: 1:4 v/v dilution in mineral oil
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:
- yes: 6 animals; applications of neat, 1:2, 1:4 and 1:8 v/v in mineral oil

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Control group: yes: vehicle control (0.5 ml mineral oil) and positive control (0.5 ml 0.3% DNCB)
- Site: dorsal midline
- Frequency of applications: weekly
- Duration: 3 weeks
- Concentrations: Undiluted for induction phases 1 and 2 and as a 1:2 v/v dilution in mineral oil for induction 3.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 13 days after last induction dose
- Exposure period: 24 hours
- Control group: vehicle control (0.5 ml mineral oil) and positive control (0.5 ml 0.2% DNCB)
- Site: on the opposite side of the dorsal midline from the induction test site
- Concentrations: 1:4 v/v in mineral oil
- Evaluation (24 hr after challenge): based on the Draize scoring method
Challenge controls:
yes
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Positive control results:
Challenge exposure for DNCB resulted in a significantly higher erythema and oedema responses than that observed in the naive challenge control group (10/10 animals; severity index 3.6 for both 24 and 48 hours).
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 mL 1:4 v/v
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 mL 1:4 v/v. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 mL 1:4 v/v
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 mL 1:4 v/v. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: no response.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5 mL 0.2% DNCB
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
well-defined to moderate to severe erythema in all 10 animals
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.5 mL 0.2% DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: well-defined to moderate to severe erythema in all 10 animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5 mL 0.2% DNCB
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight to moderate to severe response in all 10 animals
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.5 mL 0.2% DNCB. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: slight to moderate to severe response in all 10 animals.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 mL mineral oil (vehicle control)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no response
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: vehicle control. Dose level: 0.5 mL mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 mL mineral oil (vehicle control)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no response
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: vehicle control. Dose level: 0.5 mL mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no response.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under these test conditions E000014200 was not a delayed contact sensitiser.
Executive summary:

Male Hartley albino guinea pigs were dermally exposed to test article E000014200 (CAS 68475-80-9) neat at a volume of 0.5 mL for induction phases one and two and to a 1:2 v/v dilution (in mineral oil) for induction three. The test article was administered as a 1:4 v/v dilution (in mineral oil) for the challenge phase for both the induction/challenge and challenge control group animals.

Following challenge there were no responses in E000014200 or vehicle control animals whilst all 10 in the positive control group had responses.

E000014200 (CAS 68475-80-9) was not a delayed contact sensitiser and no classification is warranted under GHS/CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Non human data

CAS 68475-80-9 (E000014200): Albino guinea pigs were dermally exposed to neat E000014200 at a volume of 0.5 mL for induction phases one and two and to a 1:2 v/v dilution (in mineral oil) for induction three. The test article was administered as a 1:4 v/v dilution (in mineral oil) for the challenge phase for both the induction/challenge and challenge control group animals. Following challenge there were no responses in E000014200 or vehicle control animals whilst all 10 in the positive control group had responses (UBTL, 1990e).

The data available on marker constituents: benzene, toluene, ethylbenzene, styrene, naphthalene, and dicyclopentadiene are considered not to be skin sensitisers.

Human data

Human data identified was for benzene (Kligman, 1966). The details of the study are not further discussed in the dossier due to ethical reasons.

References

Kligman AM (1966). The identification of contact allergens by human assay.III The maximization test: a procedure for screening and rating contact sensitizers. J Int Dermatol, 47 (5), 393-409.


Migrated from Short description of key information:
Fuel Oils streams are considered not to be skin or respiratory sensitisers. Specific data for one Fuel Oils stream E000014200 (CAS 68475-80-9) indicates that it is not a skin sensitiser. The components benzene, toluene, ethylbenzene, styrene, and naphthalene are considered not to be skin sensitisers.

Justification for selection of skin sensitisation endpoint:
Information available for a representative stream and for the marker substances present indicate no potential to induce or elicit skin sensitisation, however, data on other constituents indicates potential to cause allergic reaction.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No specific animal or human data have been found with regard to respiratory sensitisation for any components within this stream.


Migrated from Short description of key information:
No data have been found concerning respiratory sensitisation and there are no indications that components within this stream are respiratory allergens.

Justification for classification or non-classification

Data on E000014200 (CAS 68475-80-9) and on the marker substances do not indicate skin sensitisation potential, however, various other components present in the streams are classified as Category 1 skin sensitisers, therefore Fuel Oils streams that contain =1% of such components should be classified as H317 under Reg (EC) 1272/2008.

Although there are no specific data on respiratory sensitisation of Fuel Oils streams or marker components there are no indications that components within this stream are respiratory allergens. It is proposed that no classification is warranted for this end-point under Reg (EC) 1272/2008.