Hydrocarbons, C9-C11, n-alkanes, isoalkanes,

Endpoint summary

Description of key information

There are no skin or eye irritation studies for the registered substance, Hydrocarbons, C9-C11 aliphatics, <2% aromatics (GS180). However, reliable skin and eye irritation studies have been conducted for two related Fischer-Tropsch process-derived hydrocarbon fractions: GS160 (C8-C11) and GS170 (C9-C12).

An in vitro skin irritation study was conducted with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) in accordance with OECD Test Guideline 439 and in compliance with GLP. The mean relative tissue viability for the test substance was below 50% after 15 minutes treatment, indicating that the substance was irritating to skin (WIL Research 2014a).

An in vivo skin irritation study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 404 and in compliance with GLP (WIL Research, 2014b). Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was concluded to be irritating to skin.

An in vitro skin irritation study was conducted with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) in accordance with OECD Test Guideline 439 and in compliance with GLP. Although the relative mean tissue viability was clearly decreased, the mean relative tissue viability for Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was just above 50%, therefore the substance was not considered to be irritating to skin on the basis of this study (WIL Research, 2014c).

However, in an in vivo skin irritation study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170), conducted in accordance with OECD Test Guideline 404 and in compliance with GLP, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was concluded to be irritating to skin (WIL Research, 2014d).

An in vitro eye irritation study was conducted with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160), in accordance with OECD Test Guideline 437 and in compliance with GLP. Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% was concluded to be not irritating to eyes (WIL Research, 2014e).

An in vivo eye irritation study with with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 405 and in compliance with GLP. Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was concluded to be not irritating to eyes (WIL Research, 2014f).

An in vitro eye irritation study was conducted with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170), in accordance with OECD Test Guideline 437 and in compliance with GLP. Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% was concluded to be not irritating to eyes (WIL Research, 2014g).

An in vivo eye irritation study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) was conducted in accordance with OECD Test Guideline 405 and in compliance with GLP. Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was concluded to be not irritating to eyes (WIL Research, 2014h).

Overall, it is concluded that both Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) and Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) are irritating to skin and not irritating to eyes. These results are read-across to Hydrocarbons, C9-C11 aliphatics, <2% aromatics (GS180).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

22 July - 21 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 substances, 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used withihn the study were between 12 and 24 weeks old.
- Weight at study initiation: Body weights were at least 1.5 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

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: From: 22 July - 21 August 2014

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

Single application.

Observation period:

14 days.

Number of animals:

3 males.

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of skin irritation observed in the first animal.

TEST SUBSTANCE PREPARATION
The test substance was applied undiluted as delivered by the sponsor.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: In the initially treated animal, the skin reactions of all visible treated sites were assessed immediately after removal of a dressing and approximately 1, 24, 48, 72 hours after the removal of the last dressing and test substance. After the 4 hours exposure in two further animals, the skin reactions were assessed approximately 1, 24, 48, 72 hours after the removal of the dressing and test substance. For the duration of the skin reactions, further observations were made 7 and 14 (maximum) days after exposure. Readings were done under true light using Philips Master TL-5 HO 49 watt/840 lamps. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of each animal serve as controls.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Irritation parameter:

erythema score

Remarks:

4-hour treatment

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 Days

Remarks on result:

positive indication of irritation

Remarks:

Bald skin and/or scaliness found at 14 Days after administration

Irritation parameter:

erythema score

Remarks:

4-hour treatment

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

bald skin on application site

Irritation parameter:

erythema score

Remarks:

4-hour treatment

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

scaliness and bald skin on application side

Irritation parameter:

edema score

Remarks:

4-hour treatment

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

4-hour treatment

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Remarks:

4-hour treatment

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

Irritation: An exposure period of three minutes to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in very slight erythema and very slight oedema in the treated skin area of the rabbit. One hour of exposure resulted in well-defined erythema and very slight oedema. Furthermore, the animal showed very superficial fissuring of the skin, bald skin and/or scaliness 7 and 14 Days after exposure. Four hours exposure to 0.5 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 Days after exposure).

Corrosion: There was no evidence of a corrosive effect on the skin.

Other effects:

Coloration/remnants: No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

Toxicity/mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

An in vivo skin irritation study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 404 and in compliance with GLP (WIL Research, 2014b). Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure). On the basis of these results, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics were concluded to be irritating to skin..

Executive summary:

Primary skin irritation/corrosion study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics in the rabbit (semi-occlusive application).

 

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

OECD No.404 (2002); "Acute Toxicity - Skin irritation"

EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion"

US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 

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

 

Initially, one rabbit was exposed to three samples of 0.5 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily for 4 days after treatment and 7 and 14 days after exposure. Based on the absence of severe skin reactions, two further animals exposed for 4 hours to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics at a later stage.

 

Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 Days after exposure). 

 

Based on the 24-72 hours mean erythema score of 2.3 in two animals and persisting skin reactions and according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) (including all amendments), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics should be classified as : skin irritant (Category 2).

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures(including all amendments), Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics should be classified as Irritant (Category 2) and labeled as H315: Causes skin irritation.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

30-Jun-2014 to 07-Jul-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 substances, 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:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN Standard ModelTM(EPISKIN-SMTM, 0.38 cm2, Lot no.:14-EKIN-024). This model is a three-dimensional human epidermis model, which consists of adult human-derived epidermal keratinocytes which have been seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. The keratinocytes were cultured for 13 days, which results in a highly differentiated and stratified epidermis model comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum.
- Tissue batch number(s): not specified
- Production date: not specified
- Shipping date: not specified
- Delivery date: not specified
- Date of initiation of testing: not specified

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: not specified
- Temperature of post-treatment incubation (if applicable): not specified

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: phosphate buffered saline

NUMBER OF REPLICATE TISSUES: triplicate tissues

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- After a 42 hour incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Cell viability was calculated for each tissue as a percentage of the mean of the negative control tissues.


PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
The in vitro skin irritation test is considered acceptable if it meets the following criteria:
a)  The absolute mean OD570(optical density at 570 nm) of the three tissues of the negative control should reasonably be within the laboratory historical control data range and the Standard Deviation value (SD) of the % viability should be ≤18.
b) The mean relative tissue viability of the positive control should be ≤40% relative to the negative control and theStandard Deviation value (SD) of the % viability should be ≤18.
c) The SD calculated from individual % tissue viabilities of the three identically treated replicates should be ≤18.
-A test substance is considered irritant in the in vitro skin irritation test if:
The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test substance and 42 hours of post incubation is
≤ 50% of the mean viability of the negative controls.
-A test substance is considered non-irritant in the in vitro skin irritation test if:
The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test substance and 42 hours of post incubation is > 50% of the mean viability of the negative controls.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 µl

NEGATIVE CONTOL:
- Amount(s) applied (volume or weight with unit): 10 µl Phosphate buffered saline

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 10 µl
- Concentration (if solution): 5% (aq) Sodium dodecyl sulphate

Duration of treatment / exposure:

Exposure: 15 minutes

Duration of post-treatment incubation (if applicable):

Post incubation period: 42 hours

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

15 minutes exposure

Value:

43

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

DEMONSTRATION OF TECHNICAL PROFICIENCY: Skin irritation is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 15 minutes treatment with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics compared to the negative control tissues was 43%.
Since the mean relative tissue viability for Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatic was below 50% after 15 minutes treatment it is considered to be irritant.
The positive control had a mean cell viability of 11% after 15 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was less than 14%, indicating that the test system functioned properly.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

An in vitro skin irritation study was conducted with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) in accordance with OECD Test Guideline 439 and in compliance with GLP. The mean relative tissue viability for the test substance was below 50% after 15 minutes treatment, indicating that the substance is irritating to skin.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

22 July - 21 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 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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used withihn the study were between 12 and 24 weeks old.
- Weight at study initiation: Body weights were at least 1.5 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

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: From: 22 July - 21 August 2014

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

Single application.

Observation period:

14 days.

Number of animals:

3 males.

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and started with the treatment of one animal (sentinel) with a stepwise exposure regime. The two other animals were exposed to the substance for four hours only and in a similar manner 2 weeks later, after considering the degree of skin irritation observed in the first animal..

TEST SUBSTANCE PREPARATION
The test substance was applied undiluted as delivered by the sponsor.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: In the initially treated animal, the skin reactions of all visible treated sites were assessed immediately after removal of a dressing and approximately 1, 24, 48, 72 hours after the removal of the last dressing and test substance. After the 4 hours exposure in two further animals, the skin reactions were assessed approximately 1, 24, 48, 72 hours after the removal of the dressing and test substance. For the duration of the skin reactions, further observations were made 7 and 14 (maximum) days after exposure. Readings were done under true light using Philips Master TL-5 HO 49 watt/840 lamps. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of each animal serve as controls.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Irritation parameter:

erythema score

Remarks:

4-hour exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 Days

Remarks on result:

positive indication of irritation

Remarks:

Scaliness found 14 Days after administration

Irritation parameter:

erythema score

Remarks:

4-hour exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

Scaliness found 14 Days after administration

Irritation parameter:

erythema score

Remarks:

4-hour exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

Scaliness and bald skin found 14 Days after administration

Irritation parameter:

edema score

Remarks:

4-hour exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Remarks:

4-hour exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Remarks:

4-hour exposure

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

Irritation: No erythema or oedema were seen in the treated skin area of the rabbit after an exposure period of three minutes to Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics. Scaliness was noted 7 Days after exposure. One hour of exposure resulted in very slight erythema and very slight oedema. Furthermore, the animal showed scaliness 7 and 14 days after exposure. Four hours exposure to 0.5 mL of Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to severe oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, bald skin and/or scaliness were present from 72 hours after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure).

Corrosion: There was no evidence of a corrosive effect on the skin.

Other effects:

Coloration/remnants: No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

Toxicity/mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

An in vivo skin irritation study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) was conducted in accordance with OECD Test Guideline 404 and in compliance with GLP. Exposure to Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to severe oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, bald skin and/or scaliness were present from 72 hours after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure). On the basis of these results, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics were concluded to be irritating to skin.

Executive summary:

Primary skin irritation/corrosion study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics in the rabbit (semi-occlusive application).

 

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

OECD No.404 (2002); "Acute Toxicity - Skin irritation"

EC, No 440/2008; B4: "Acute Toxicity: Dermal Irritation/Corrosion"

US EPA, OPPTS 870.2500 (1998), Acute Dermal Irritation 

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

 

Initially, one rabbit was exposed to three samples of 0.5 mL of Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily for 4 days after treatment and 7 and 14 days after exposure. Based on the absence of severe skin reactions, two further animals exposed for 4 hours to Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics at a later stage.

 

Exposure to Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to severe oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, bald skin and/or scaliness were present from 72 hours after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure).

  

Based on the persisting skin reactions (scaliness and/or bald skin) and according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007)(including all amendments), Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics should be classified as skin irritant (Category 2).

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures(including all amendments), Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics should be classified as Irritant (Category 2) and labeled as H315: Causes skin irritation.

Reference 4

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

30-Jun-2014 to 22-Sep-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:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EPISKIN Standard ModelTM (EPISKIN-SMTM, 0.38 cm2, Lot no.: 14-EKIN-035). This model is a three-dimensional human epidermis model, which consists of adult human-derived epidermal keratinocytes which have been seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. The keratinocytes were cultured for 13 days, which results in a highly differentiated and stratified epidermis model comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum.

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: phosphate buffered saline

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- After a 42 hour incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Cell viability was calculated for each tissue as a percentage of the mean of the negative control tissues.


NUMBER OF REPLICATE TISSUES: triplicate tissues

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
The in vitro skin irritation test is considered acceptable if it meets the following criteria:
a)  The absolute mean OD570 (optical density at 570 nm) of the three tissues of the negative control should reasonably be within the laboratory historical control data range and the Standard Deviation value (SD) of the % viability should be ≤18.
b) The mean relative tissue viability of the positive control should be ≤40% relative to the negative control and the Standard Deviation value (SD) of the % viability should be ≤18.
c) The SD calculated from individual % tissue viabilities of the three identically treated replicates should be ≤18.
- A test substance is considered irritant in the in vitro skin irritation test if:
The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test substance and 42 hours of post incubation is
≤ 50% of the mean viability of the negative controls.
- A test substance is considered non-irritant in the in vitro skin irritation test if:
The relative mean tissue viability of three individual tissues after 15 minutes of exposure to the test substance and 42 hours of post incubation is > 50% of the mean viability of the negative controls.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 µl

NEGATIVE CONTOL:
- Amount(s) applied (volume or weight with unit): 10 µl Phosphate buffered saline

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 10 µl
- Concentration (if solution): 5% (aq) Sodium dodecyl sulphate

Duration of treatment / exposure:

Exposure: 15 minutes

Duration of post-treatment incubation (if applicable):

Post incubation period: 42 hours

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

15 minutes exposure

Value:

59

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

DEMONSTRATION OF TECHNICAL PROFICIENCY: Skin irritation is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 15 minutes treatment with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics compared to the negative control tissues was 59%. Although the relative mean tissue viability was clearly decreased, the mean relative tissue viability for Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was just above 50%. Therefore, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics is considered to be non-irritant.
 
The positive control had a mean cell viability of 13% after 15 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was less than 9%, indicating that the test system functioned properly.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Interpretation of results:

GHS criteria not met

Conclusions:

An in vitro skin irritation study was conducted with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) in accordance with OECD Test Guideline 439 and in compliance with GLP. Although the relative mean tissue viability was clearly decreased, the mean relative tissue viability for Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was just above 50%, therefore the substance is not considered to be irritating to skin on the basis of this study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

15 July - 07 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 substances, 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used withihn the study were between 12 and 24 weeks old.
- Weight at study initiation: Body weights were at least 1.5 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

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: From: 15 July - 07 August 2014

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL- Amount applied: 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.

Number of animals or in vitro replicates:

3 males

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. Readings were done under true light using Philips Master TL-5 HO 49 watt/840. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 405.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation: Instillation of 0.1 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness in all animals and discharge in one animal. The irritation had completely resolved within 24 hours in all animals. No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion: There was no evidence of ocular corrosion.

Other effects:

Colouration/Remnants: No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

An in vivo eye irritation study with with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 405 and in compliance with GLP. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness in all animals and discharge in one animal. The irritation had completely resolved within 24 hours in all animals. On the basis of these results, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was concluded to be not irritating to eyes.

Executive summary:

Acute eye irritation/corrosion study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics in the rabbit.

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

OECD No.405 (2012) "Acute Eye Irritation / Corrosion"

EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

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

 

Single samples of 0.1 mL of Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

 

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness in all animals and discharge in one animal. The irritation had completely resolved within 24 hours in all animals.

 

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 eye irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011)(including all amendments),

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

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

08-Jul-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 substances, 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 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

cattle

Details on test animals or tissues and environmental conditions:

Bovine eyes from young cattle were obtained from the slaughterhouse, where the eyes were excised by a slaughterhouse employee as soon as possible after slaughter.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µl per cornea

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount(s) applied (volume or weight with unit): 750 µl per cornea
Concentration (if solution): 20% (w/v) Imidazole

Duration of treatment / exposure:

10 minutes

Details on study design:

TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 10 minutes

SCORING SYSTEM:
- After exposure the cornea was thoroughly rinsed to remove the test substance and incubated for 2 hours with fresh medium followed by opacity measurement and the permeability of the corneas was determined after a 90 minutes incubation period with sodium fluorescein.

- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).


TOOL USED TO ASSESS SCORE:
- opacitymeter and microplate reader

DATA EVALUATION:
In vitro score range UN GHS
≤ 3 No Category
> 3; ≤ 55 No prediction can be made
>55 Category 1

Irritation parameter:

in vitro irritation score

Run / experiment:

10 minutes exposure

Value:

-0.1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

DEMONSTRATION OF TECHNICAL PROFICIENCY: The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 141 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Interpretation of results:

GHS criteria not met

Conclusions:

An in vitro eye irritation study was conducted with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160), in accordance with OECD Test Guideline 437 and in compliance with GLP. Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.1 after 10 minutes of treatment. The BCOP test did not indicate an irritancy potential based on either the opacity or permeability endpoints.

Executive summary:

 

 

.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

15 July - 08 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: Animals used withihn the study were between 12 and 24 weeks old.
- Weight at study initiation: Body weights were at least 1.5 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

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: From: 15 July - 08 August 2014

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL- Amount applied: 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance

Number of animals or in vitro replicates:

3 males

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner three weeks later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam (Metacam®, Boehringer Vetmed GmbH, Ingelheim/Rhein, Germany) 0.5 mg/kg were administered by subcutaneous injection. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. Readings were done under true light using Philips Master TL-5 HO 49 watt/840. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 405.

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation: Instillation of 0.1 mL of Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness and discharge in all animals. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals. No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion: There was no evidence of ocular corrosion.

Other effects:

Colouration/Remnants: No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity/Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

An in vivo eye irritation study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) was conducted in accordance with OECD Test Guideline 405 and in compliance with GLP. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge in all animals. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals. On the basis of these results, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was concluded to be not irritating to eyes.

Executive summary:

Acute eye irritation/corrosion study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics in the rabbit.

 

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

OECD No.405 (2012) "Acute Eye Irritation / Corrosion"

EC, No 440/2008, B5: "Acute Toxicity: Eye Irritation/Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

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

 

Single samples of 0.1 mL of Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours after instillation.

 

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge in all animals. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals.

 

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 eye irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011)(including all amendments),

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

Reference 4

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

08-Jul-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 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

cattle

Details on test animals or tissues and environmental conditions:

Bovine eyes from young cattle were obtained from the slaughterhouse, where the eyes were excised by a slaughterhouse employee as soon as possible after slaughter.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µl per cornea

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount(s) applied (volume or weight with unit): 750 µl per cornea
Concentration (if solution): 10% (w/v) Benzalkonium Chloride

Duration of treatment / exposure:

10 minutes

Details on study design:

TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 10 minutes

SCORING SYSTEM:
- After exposure the cornea was thoroughly rinsed to remove the test substance and incubated for 2 hours with fresh medium followed by opacity measurement and the permeability of the corneas was determined after a 90 minutes incubation period with sodium fluorescein.

- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).


TOOL USED TO ASSESS SCORE:
- opacitymeter and microplate reader

DATA EVALUATION:
In vitro score range UN GHS
≤ 3 No Category
> 3; ≤ 55 No prediction can be made
>55 Category 1

Irritation parameter:

in vitro irritation score

Run / experiment:

10 minutes exposure

Value:

-0.1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

DEMONSTRATION OF TECHNICAL PROFICIENCY:
The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 141 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Interpretation of results:

GHS criteria not met

Conclusions:

An in vitro eye irritation study was conducted with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170), in accordance with OECD Test Guideline 437 and in compliance with GLP. Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.1 after 10 minutes of treatment. The BCOP test did not indicate an irritancy potential based on either the opacity or permeability endpoints.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no skin or eye irritation studies for the registered substance, Hydrocarbons, C9-C11 aliphatics, <2% aromatics (GS180). However, reliable skin and eye irritation studies have been conducted for two related Fischer-Tropsch process-derived hydrocarbon fractions: GS160 (C8-C11) and GS170 (C9-C12).

Skin Irritation

An in vitro skin irritation study was conducted with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) in accordance with OECD Test Guideline 439 and in compliance with GLP. The mean relative tissue viability for the test substance was below 50% after 15 minutes treatment, indicating that the substance is irritating to skin (WIL Research 2014a).

An in vivo skin irritation study with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 404 and in compliance with GLP (WIL Research, 2014b). Exposure to Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to moderate oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, balding and/or scaliness were present from 7 days after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure). On the basis of these results, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was concluded to be irritating to skin.

An in vitro skin irritation study was conducted with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) in accordance with OECD Test Guideline 439 and in compliance with GLP. Although the relative mean tissue viability was clearly decreased, the mean relative tissue viability for Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was just above 50%, therefore the substance was not considered to be irritating to skin on the basis of this study (WIL Research, 2014c).

However, in an in vivo skin irritation study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170), conducted in accordance with OECD Test Guideline 404 and in compliance with GLP, Exposure to Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics resulted in well-defined or moderate to severe erythema and slight to severe oedema in the treated skin areas of the rabbits. Reduced flexibility, very superficial fissuring, bald skin and/or scaliness were present from 72 hours after exposure onwards. Scaliness and/or bald skin persisted until termination (14 days after exposure). On the basis of these results, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was concluded to be irritating to skin (WIL Research, 2014d).

Eye irritation

An in vitro eye irritation study was conducted with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160), in accordance with OECD Test Guideline 437 and in compliance with GLP. Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.1 after 10 minutes of treatment. The BCOP test did not indicate an irritancy potential based on either the opacity or permeability endpoints (WIL Research, 2014e).

An in vivo eye irritation study with with Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics (GS160) was conducted in accordance with OECD Test Guideline 405 and in compliance with GLP. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness in all animals and discharge in one animal. The irritation had completely resolved within 24 hours in all animals. On the basis of these results, Hydrocarbons, C8-C11, n-alkanes, isoalkanes, <2% aromatics was concluded to be not irritating to eyes (WIL Research, 2014f).

An in vitro eye irritation study was conducted with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170), in accordance with OECD Test Guideline 437 and in compliance with GLP. Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.1 after 10 minutes of treatment. The BCOP test did not indicate an irritancy potential based on either the opacity or permeability endpoints (WIL Research, 2014g).

An in vivo eye irritation study with Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics (GS170) was conducted in accordance with OECD Test Guideline 405 and in compliance with GLP. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge in all animals. The irritation had completely resolved within 24 hours in one animal and within 48 hours in the other two animals. On the basis of these results, Hydrocarbons, C9-C12, n-alkanes, isoalkanes, <2% aromatics was concluded to be not irritating to eyes (WIL Research, 2014h).

Justification for classification or non-classification

SKIN IRRITATION:

Based on the available in vitro and in vivo skin irritation 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, it is concluded that Hydrocarbons C9-C11, n-alkanes, isoalkanes, <2% aromatics require classification for skin irritation Category 2, H315: "Causes skin irritation" according to Regulation (EC) No 1272/2008.

 

EYE IRRITATION:

Based on the available in vitro and in vivo eye irritation 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, it is concluded that Hydrocarbons C9-C11, n-alkanes, isoalkanes, <2% aromatics does not require classification for eye irritation according to Regulation (EC) No 1272/2008.

RESPIRATORY IRRITATION:

There are no studies that warrant classification as a respiratory irritant according to Regulation (EC) No 1272/2008.