Registration Dossier

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Description of key information

There are no skin sensitisation studies for the registered substance, Hydrocarbons, C9-C11 aliphatics, <2% aromatics (GS180). However, reliable guinea pig maximisation tests have been conducted in accordance with OECD Test Guideline 406 and in compliance with GLP for two related Fischer-Tropsch process-derived hydrocarbon fractions: GS160 (C8-C11) and GS170 (C9-C12).

In a guinea pig maximisation test, conducted in accordance with OECD Test Guideline 406 and in compliance with GLP (WIL Research, 2014i), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was concluded to be not sensitising to skin.

In a guinea pig maximisation test, conducted in accordance with OECD Test Guideline 406 and in compliance with GLP (WIL Research, 2014j), Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was concluded to be not sensitising to skin.

These studies cover the entire carbon number range relevant for the registration substance and are therefore used as weight of evidence to demonstrate that constituents of these substances are not sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
01 July - 15 August 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
1. Hypothesis for the analogue approach:
The hypothesis for the analogue approach is that both the registration substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics (target substance), and the test substance, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (source substance), are produced from the same Fischer-Tropsch substance, GTL Gasoil, by fractional distillation. The substances are C9-C14 Aliphatics [≤2% Aromatics] Hydrocarbon Solvents.

The source substances contain the all of the constituents of the target substance. The substances have constituents that are part of the same homologous series and have many constituents in common. The substances therefore have qualitatively similar properties (RAAF Scenario 2 applies).

2. Source and target chemical(s)
The source substance Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics is composed of linear, branched and cyclic hydrocarbons of chain length C8-C11

The target substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics, is composed of linear, branched and cyclic hydrocarbons of chain length C9-C11.

3. Analogue approach justification
The constituents of the source and target substances are all hydrocarbons. Identical constituents have identical toxicological properties. The source substances cover the full carbon chain length of the target substance.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(2003)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable guinea pig maximisation test that followed sound scientific principles.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’arbresle Cedex, France.
- Age at study initiation: Young adult animals (approx. 4 weeks old)
- Weight at study initiation: 277 g
- Housing: Group housing of maximally 5 animals per labeled cage.
- Diet (e.g. ad libitum): Complete breeding diet for guinea pigs (SSNIFF® MS-Z, V2273; SSNIFF® Spezialdiäten GmbH, Soest, Germany). Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least twice a week.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

IN-LIFE DATES: 01 July - 15 August 2014
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
100, 50, 20 and 10% for the intradermal induction and for the epidermal induction.
50% for the challenge phase.
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
100, 50, 20 and 10% for the intradermal induction and for the epidermal induction.
50% for the challenge phase.
No. of animals per dose:
Test animals: 10
Control animals: 5
Details on study design:
RANGE FINDING TESTS: (4 animals, age: between 4 and 9 weeks old)

Intradermal injections:
A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be injected. Each of two animals received two different concentrations in duplicate (0.1 mL/site) in the clipped scapular region. The injection sites were assessed for irritation 24 and 48 hours after treatment.
For results see appendix.

Epidermal application:
A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be applied. Two different concentrations were applied (0.5 mL each) per animal to the clipped flank, using Metalline patches# (2x3 cm) mounted on Medical tape# which were held in place with Micropore tape# and subsequently Coban elastic bandage#. The animals receiving intradermal injections were treated with the lowest concentrations and two further animals with the highest concentrations. After 24 hours, the dressing was removed and the skin cleaned of residual test substance using water. The treated skin areas were assessed for irritation 24 and 48 hours after exposure.
#. Suppliers: Lohmann & Rauscher B.V., Almere, The Netherlands (Metalline) and 3M, St. Paul, Minnesota, U.S.A. (Medical tape, Micropore and Coban).
For results see appendix.

MAIN STUDY
INDUCTION - Experimental animals
Day 1 The scapular region was clipped and three pairs of intradermal injections (0.1 mL/site) were made in this area as follows:
A) A 1:1 w/w mixture of Freunds' Complete Adjuvant (Difco, Detroit, U.S.A.) with water for injection (B.Braun Melsungen AG, Melsungen. Germany).
B) The test substance at a 20% concentration.
C) A 1:1 w/w mixture of the test substance, at twice the concentration used in (B) and Freunds' Complete Adjuvant.
Note: One of each pair was on each side of the midline and from cranial A) to caudal C).
Day 3 The dermal reactions caused by the intradermal injections were assessed for irritation.
Day 8 The scapular area between the injection sites was clipped and subsequently treated with 0.5 mL of a 50% test substance concentration using a Metalline patch (2x3 cm) mounted on Medical tape, which was held in place with Micropore tape and subsequently Coban elastic bandage. The dressing was removed after 48 hours exposure, the skin cleaned of residual test substance using water and the dermal reactions caused by the epidermal exposure were assessed for irritation.
INDUCTION - Control animals
The control animals were treated as described for the experimental animals except that, instead of the test substance, vehicle alone was administered.

CHALLENGE - All animals
Day 22 One flank of all animals was clipped and treated by epidermal application of a 50% test substance concentration and the vehicle (0.1 mL each), using Patch Test Plasters (Curatest®, Lohmann, Almere, The Netherlands). The patches were held in place with Micropore tape and subsequently Coban elastic bandage. The dressing was removed after 24 hours exposure and the skin cleaned of residual test substance and vehicle using water. The treated sites were assessed for challenge reactions 24 and 48 hours after removal of the dressing.
After termination, animals were sacrificed using isoflurane (Abbott B.V., Hoofddorp, The Netherlands) and an intra-peritoneal injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).
Challenge controls:
Not applicable
Positive control substance(s):
yes
Remarks:
(the results of the latest reliability check, performed in July/August 2014 with Alpha- Hexylcinnamaldehyde, are reported)
Positive control results:
The latest reliability check (performed less than 6 months before the study) shows a sensitisation rate of 90%.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% test substance in corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% test substance in corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% test substance in corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance in corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
20% alpha-hexylcinnamicaldehyde
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
Positive control reliability check carried out July/August 2014
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
20% alpha-hexylcinnamicaldehyde
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
20% alpha-hexylcinnamicaldehyde Positive control reliability check carried out July/August 2014

Signs of irritation during induction:
For skin effects caused by the intradermal injections and epidermal exposure during the induction phase see appendix.

Evidence of sensitisation of the challenge concentration:

No skin reactions were evident after the challenge exposure in the experimental and control animals.

Toxicity / Mortality: No mortality occurred and no symptoms of systemic toxicity were observed in the animals of the main study.

Body weights: Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea pig maximisation test, conducted in accordance with OECD 406 and GLP, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was tested at a challenge concentration of 50% v/v in corn oil. Intradermal induction was performed at a concentration of 20% v/v, and topical induction 50% test substance in corn oil. No skin reactions were observed in any test or control group animals at challenge indicating that the substance is not sensitising to skin.

Executive summary:

Assessment of Contact Hypersensitivity to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics in the Albino Guinea Pig (Maximization Test).

The study was carried out based on the guidelines described in:

OECD No. 406 (1992) "Skin Sensitization"

EC No 440/2008; B6: "Skin Sensitization: Guinea-Pig Maximization Test (GPMT)"

EPA OPPTS 870.2600 (2003) “Skin Sensitization”

JMAFF Guidelines (2000), including the most recent revisions.

The study was based on the method described by Magnusson and Kligman, "Allergic Contact Dermatitis in the Guinea Pig - Identification of Contact Allergens" (1970).

Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, ten experimental animals were intradermally injected with a 20% concentration and epidermally exposed to a 50% concentration. Five control animals were similarly treated, but with vehicle alone (corn oil). Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle. No skin reactions were evident after the challenge exposure in the experimental and control animals. There was no evidence that Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics had caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in response to a 50% test substance concentration in the challenge phase. This result indicates a sensitization rate of 0 per cent.

Based on these results Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) (including all amendments),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
01 July - 15 August 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
1. Hypothesis for the analogue approach:
The hypothesis for the analogue approach is that both the registration substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics (target substance), and the test substance, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (source substance), are produced from the same Fischer-Tropsch substance, GTL Gasoil, by fractional distillation. The substances are C9-C14 Aliphatics [≤2% Aromatics] Hydrocarbon Solvents.

The source substances contain the all of the constituents of the target substance. The substances have constituents that are part of the same homologous series and have many constituents in common. The substances therefore have qualitatively similar properties (RAAF Scenario 2 applies).

2. Source and target chemical(s)
The source substance Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics, is composed of linear, branched and cyclic hydrocarbons of chain length C9-C12.

The target substance, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics, is composed of linear, branched and cyclic hydrocarbons of chain length C9-C11.

3. Analogue approach justification
The constituents of the source and target substances are all hydrocarbons. Identical constituents have identical toxicological properties. The source substances cover the full carbon chain length of the target substance.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Version / remarks:
(2003)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Acceptable guinea pig maximisation test that followed sound scientific principles.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’arbresle Cedex, France.
- Age at study initiation: Young adult animals (approx. 5-6 weeks old)
- Weight at study initiation: approx 396 g.
- Housing: Group housing of maximally 5 animals per labeled cage.
- Diet (e.g. ad libitum): Complete breeding diet for guinea pigs (SSNIFF® MS-Z, V2273; SSNIFF® Spezialdiäten GmbH, Soest, Germany). Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least twice a week.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

IN-LIFE DATES: 01 July - 15 August 2014
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
100, 50, 20 and 10% for the intradermal induction and for the epidermal induction.
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
50% for the first challenge phase, 20% for the second challenge phase.
No. of animals per dose:
Test animals: 10
Control animals: 5
Details on study design:
RANGE FINDING TESTS: (4 animals, age: between 4 and 9 weeks old)

Intradermal injections:
A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be injected. Each of two animals received two different concentrations in duplicate (0.1 mL/site) in the clipped scapular region. The injection sites were assessed for irritation 24 and 48 hours after treatment.
For results see appendix.

Epidermal application:
A series of four test substance concentrations was used, the highest concentration being the maximum concentration that could technically be applied. Two different concentrations were applied (0.5 mL each) per animal to the clipped flank, using Metalline patches# (2x3 cm) mounted on Medical tape# which were held in place with Micropore tape# and subsequently Coban elastic bandage#. The animals receiving intradermal injections were treated with the lowest concentrations and two further animals with the highest concentrations. After 24 hours, the dressing was removed and the skin cleaned of residual test substance using water. The treated skin areas were assessed for irritation 24 and 48 hours after exposure.
#. Suppliers: Lohmann & Rauscher B.V., Almere, The Netherlands (Metalline) and 3M, St. Paul, Minnesota, U.S.A. (Medical tape, Micropore and Coban).
For results see appendix.

MAIN STUDY
INDUCTION - Experimental animals
Day 1 The scapular region was clipped and three pairs of intradermal injections (0.1 mL/site) were made in this area as follows:
A) A 1:1 w/w mixture of Freunds' Complete Adjuvant (Difco, Detroit, U.S.A.) with water for injection (B.Braun Melsungen AG, Melsungen. Germany).
B) The test substance at a 20% concentration.
C) A 1:1 w/w mixture of the test substance, at twice the concentration used in (B) and Freunds' Complete Adjuvant.
Note: One of each pair was on each side of the midline and from cranial A) to caudal C).
Day 3 The dermal reactions caused by the intradermal injections were assessed for irritation.
Day 8 The scapular area between the injection sites was clipped and subsequently treated with 0.5 mL of a 100% test substance concentration using a Metalline patch (2x3 cm) mounted on Medical tape, which was held in place with Micropore tape and subsequently Coban elastic bandage.
The dressing was removed after 48 hours exposure, the skin cleaned of residual test substance using water and the dermal reactions caused by the epidermal exposure were assessed for irritation.
INDUCTION - Control animals
The control animals were treated as described for the experimental animals except that, instead of the test substance, vehicle alone was administered.

CHALLENGE - All animals
Day 21 One flank of all animals was clipped and treated by epidermal application of a 50% test substance concentration and the vehicle (0.1 mL each), using Patch Test Plasters (Curatest®, Lohmann, Almere, The Netherlands). The patches were held in place with Micropore tape and subsequently Coban elastic bandage.
The dressing was removed after 24 hours exposure and the skin cleaned of residual test substance and vehicle using water. The treated sites were assessed for challenge reactions 24 and 48 hours after removal of the dressing.
Day 28 A re-challenge was conducted approximately one week after the first challenge to clarify the results in the first challenge. The contralateral flank of all animals was similarly treated, with a 20% test substance concentration and the vehicle.
After termination, animals were sacrificed using isoflurane (Abbott B.V., Hoofddorp, The Netherlands) and an intra-peritoneal injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).
Challenge controls:
Not applicable
Positive control substance(s):
yes
Remarks:
(the results of the latest reliability check, performed in July/August 2014 with Alpha- Hexylcinnamaldehyde, are reported)
Positive control results:
The latest reliability check (performed less than 6 months ago) shows a sensitisation rate of 90%.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% in corn oil
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% in corn oil
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% test substance in corn oil
No. with + reactions:
2
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance in corn oil
No. with + reactions:
1
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
First challenge
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
20% test substance in corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
20% test substance in corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
20% test substance in corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
20% test substance in corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
corn oil
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Remarks:
Second challenge
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
20% alpha-hexylcinnamicaldehyde
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
20% alpha-hexylcinnamicaldehyde Positive control reliability check carried out July/August 2014

Signs of irritation during induction:

For skin effects caused by the intradermal injections and epidermal exposure during the induction phase see appendix.

Evidence of sensitisation of the challenge concentration:

First challenge: Skin reactions of grade 1, were observed in two experimental animals and two control animals in response to the 50% test substance concentration.

Second challenge: It could not be decided whether the substance is a sensitizer or not since comparable skin reactions were observed in both experimental and control animals. Therefore, a second challenge was performed one week later with a lower concentration of 20% in order to avoid skin reactions in the controls.

No skin reactions were evident after the challenge exposure in the experimental and control animals.

Toxicity / Mortality: No mortality occurred and no symptoms of systemic toxicity were observed in the animals of the main study.

Body weights: Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea pig maximisation test, conducted in accordance with OECD 406 and GLP, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was tested at a challenge concentration of 20% v/v in corn oil. Intradermal induction was performed at a concentration of 20% v/v, and topical induction used undiluted test substance. No skin reactions were observed in any test or control group animals at challenge indicating that the substance is not sensitising to skin.
Executive summary:

Assessment of Contact Hypersensitivity to Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics in the Albino Guinea Pig (Maximization Test).

The study was carried out based on the guidelines described in:

OECD No. 406 (1992) "Skin Sensitization"

EC No 440/2008; B6: "Skin Sensitization: Guinea-Pig Maximization Test (GPMT)"

EPA OPPTS 870.2600 (2003) “Skin Sensitization”

JMAFF Guidelines (2000), including the most recent revisions.

The study was based on the method described by Magnusson and Kligman, "Allergic Contact Dermatitis in the Guinea Pig - Identification of Contact Allergens" (1970).

Test substance concentrations selected for the main study were based on the results of a preliminary study.

In the main study, ten experimental animals were intradermally injected with a 20% concentration and epidermally exposed to a 100% concentration. Five control animals were similarly treated, but with vehicle alone (corn oil).

Two weeks after the epidermal application all animals were challenged with a 50% test substance concentration and the vehicle. A second challenge was performed one week later with the test substance concentration 20% and the vehicle.

First Challenge: Skin reactions of grade 1, were observed in two experimental animals and two control animals in response to the 50% test substance concentration.

Second challenge: It could not be decided whether the substance is a sensitizer or not since comparable skin reactions were observed in both experimental and control animals. Therefore, a second challenge was performed one week later with a lower concentration of 20% in order to avoid skin reactions in the controls. No skin reactions were evident after the challenge exposure in the experimental and control animals.

There was no evidence that Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics had caused skin hypersensitivity in the guinea pig, since no responses were observed in the experimental animals in response to a 20% test substance concentration in the challenge phase. This result indicates a sensitization rate of 0 per cent.

Based on these results Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) (including all amendments),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

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

There are no skin sensitisation studies for the registered substance, Hydrocarbons, C9-C11 aliphatics, <2% aromatics (GS180). However, reliable guinea pig maximisation tests have been conducted in accordance with OECD Test Guideline 406 and in compliance with GLP for two related Fischer-Tropsch process-derived hydrocarbon fractions: GS160 (C8-C11) and GS170 (C9-C12).

In a guinea pig maximisation test, conducted in accordance with OECD Test Guideline 406 and in compliance with GLP (WIL Research, 2014i), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was tested at a challenge concentration of 50% v/v in corn oil. Intradermal induction was performed at a concentration of 20% v/v, and topical induction 50% test substance in corn oil. No skin reactions were observed in any test or control group animals at challenge indicating that the substance is not sensitising to skin.

In a guinea pig maximisation test, conducted in accordance with OECD Test Guideline 406 and in compliance with GLP (WIL Research, 2014j), Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was tested at a challenge concentration of 20% v/v in corn oil. Intradermal induction was performed at a concentration of 20% v/v, and topical induction used undiluted test substance. No skin reactions were observed in any test or control group animals at challenge indicating that the substance is not sensitising to skin.

These studies cover the entire carbon number range relevant for the registration substance and are therefore used as weight of evidence to demonstrate that constituents of these substances are not sensitising.

Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics is not considered to be a skin sensitizer based on read across data available from Human Repeated Insult Patch Tests (HRIPT).

 

A key human skin patch test (ExxonMobil Corp, 1988c) was conducted to determine the potential of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics to cause dermal irritation and sensitization in humans with or without UV irradiation. Twenty-eight humans were exposed to the test material. Dermal examinations occurred after exposures (day 1 and day 2) and then at 24h, 48h, and 72h post exposure. Dermal irritation and damage was assessed and scored according to a modified Draize scale. The most severe reaction noted in all experimental paradigms was noted as a "1" or slight erythema. The test material did not elicit any effects which could be construed as a characteristic of a phototoxic propensity or of a primary irritant. MRD-88-296 showed no evidence of being a photo contact allergen and no evidence of being either a primary irritant or a contact allergen. Based on these data and results, Hydrocarbons, C10-C12, isoalkanes, <2% aromatics would not be classified as a dermal irritant or as a dermal sensitizer.

 

Another key human skin patch test (ExxonMobil Corp, 1988d) was conducted to determine the potential of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics to cause dermal irritation and sensitization in humans. The induction applications were made to a site on the back (0.2 ml test material, neat) using an occlusive patch.  The patch held the material in place for 24 hours at which time, the subjects returned for an evaluation of the application site and for new test material to be applied.  Due to 35 subjects developing an erythema score between 3 and 5, it was decided that a 50/50 w/w test sample (in USP petrolatum) would be applied to an alternate test site using a semi-occlusive patch for the duration of the experiment after subjects were treatment-free for one week.  Applications were held in place via a semi-occlusive patch for 24 hours and subjects were examined daily for dermal effects before receiving a fresh application of 50/50 w/w test material for a total of 9 additional applications.  A 3-5 day rest period followed the last induction application.   A challenge application was applied to a naïve site on the back that consisted of a 50% (w/w) of test material preparation held in place by a semi-occlusive patch for a total of 4- 24 hour applications. 

There was no indication that the test material possesses a skin-sensitizing propensity as there was no recordable skin irritation noted in any of the patients.  When the test material, neat was applied under occluded conditions, the severe irritation that occurred indicates that it would be considered a dermal irritant.  However, the occlusion of the test material prevents evaporation and changes the permeability of the dermis.  In order to determine the irritancy of the test material in a relevant paradigm, a 50% (w/w) solution of the test material was applied under a semi-occluded patch.  No significant dermal irritation was noted and thus, Hydrocarbons, C10-C12, isoalkanes, <2% aromatics would not be considered a dermal irritant.

In a third key study (ExxonMobil Corp., 1962e), Hydrocarbons, C10–C12, isoalkanes, < 2% aromatics and Hydrocarbons, C11–C12, isoalkanes, < 2% aromatics were evaluated for skin irritating properties in humans following a simulated use patch technique. A total of 101 subjects, including males and females, participated in the program. Each subject was patch tested before and after a three-week simulated use period. Under conditions and procedures used in the investigation the test materials will not be considered primary skin irritants under semi-occluded conditions. None of the test materials produced skin fatigue on repeated daily application during a three-week simulated use period. None of the test materials were skin sensitizers.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available skin sensitisation studies with related Fischer-Tropsch process-derived products, Hydrocarbons C8-C11, n-alkanes, isoalkanes, <2% aromatics and Hydrocarbons C9-C12, n-alkanes, isoalkanes, <2% aromatics, Hydrocarbons C9-C11, n-alkanes, isoalkanes, <2% aromatics is not classified for skin sensitisation according to Regulation (EC) No 1272/2008.