C8-C26 branched and linear hydrocarbons – Distillates

Endpoint summary

Description of key information

- Skin irritation / corrosion: not irritating (based on results of three reliable OECD 404 studies for related substances, covering the carbon numbers in the range C12-C50).
- Eye irritation: not irritating (based on results of three reliable OECD 405 studies for related substances, covering the carbon numbers in the range C12-C50)
- Respiratory irritation: The conclusion of not irritant to the respiratory tract is based on the absence of significant irritating effects on other membranes, specifically the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study on supporting substance (with limited range, C8-C12) conducted in compliance with GLP; acceptable, well-documented study report which meets basic scientific principles.

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 OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young rabbits, approximately 3 months old
- Weight at study initiation: Individual body weights were recorded for each animal at test begin (2.29 to 2.62 kg) and at least weekly thereafter.
- Housing: Animals were individually housed in suspended stainless steel cages mounted in mobile batteries.
- Diet (e.g. ad libitum): Free access to standard pelleted diet.
- Water (e.g. ad libitum): Free access (ad libitum)
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (range 15 to 23°C)
- Humidity (%): 55% R.H. (range 40% to 70% R.H.
- Air changes (per hr): Al least 10 complete air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h : 12 h

IN-LIFE DATES:
From: 5 March 1996 to 20 March 1996

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): pure test substance


VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used
- Concentration (if solution): no vehicle used
- Lot/batch no. (if required): no vehicle used
- Purity: no vehicle used

Duration of treatment / exposure:

4 h

Observation period:

16 d

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure:
Test area 6x6 cm, single dose was applied to skin (3x2 cm)
- % coverage:
Not applicable
- Type of wrap if used:
Treated skin was covered by an unmedicated gauze patch (3x2 cm)


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
Dressings were removed after exposure and treatment sites gently washed with warm water and dried with paper tissues.
- Time after start of exposure:
After 4 hours

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 3 days

Score:

0.89

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: max duration of effect: 10 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 3 days

Score:

0.17

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: max duration of effect: 7 days

Other effects:

Exfoliation was evident at all test sites from Day 7 until termination on Day 16. The exfoliation observed at termination of the study probably reflected a recovery process from a drying effect of the test material.

Summary-Table of Results: Mean values for erythema and oedema (24, 48 and 72 hours after removal of dressings)

Animal number and Sex	Erythema		Oedema
	Test	Control	Test	Control
32TD944, Female	1.0	0.0	0.0	0.0
32TD945, Female	0.3	0.0	1.0	0.0
32TD946, Female	1.0	0.0	0.0	0.0
32TD947, Female	1.0	0.0	0.0	0.0
32TD948, Female	1.0	0.0	0.0	0.0
32TD949, Female	1.0	0.0	0.0	0.0
Overall Mean Score	0.9	0.0	0.2	0.0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear', an analogue to 'Distillates (Fischer-Tropsch), C8-26-branched and linear' was considered to be slightly irritating to rabbit skin.
According to Annex VI of Council Directive 67/548/EEC 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' is unclassified with regards to skin irritation.
Finally, the related substance 'Distillates (Fischer-Tropsch), C8-26-branched and linear' should also not be classified. Although the test material is not classified the following additional classification makes sense: R66 (EUH066) Repeated exposure may cause skin dryness or cracking.

Executive summary:

The potential of the test item to cause skin irritation on New Zealand White rabbits was investigated according to OECD guideline 404 and US-EPA OTS 798.4470 (Skin irritation). A volume of 0.5 mL test item was applied to six female rabbits.

Under the conditions of this test, the test item was considered to be slightly irritating to the skin. However, the test material did not meet the criteria for classifcation as a skin irritant according to EU CLP Regulation.

Finally, the analogue 'Distillates (Fischer-Tropsch), full range, C8 -26-branched and linear' should also be slightly irritating to the skin and should also not be classified. Although the test material is not classified, the following additional classification makes sense: R66 (EUH066) Repeated exposure may cause skin dryness or cracking.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study on supporting substance (with limited range, C8-C12) conducted in compliance with GLP and acceptable, well-documented study report which meets basic scientific principles

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 OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation:
Young rabbits, 4 to 5 months old
- Weight at study initiation:
Individual body weights were recorded for each animal at test begin (2.28 to 3.54 kg) and at least weekly thereafter.
- Housing:
Animals were individually housed in suspended stainless steel cages mounted in mobile batteries.
- Diet (e.g. ad libitum):
Free access to standard pelleted diet.
- Water (e.g. ad libitum):
Free access (ad libitum)
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
18°C (range 15 to 23°C)
- Humidity (%):
55% R.H. (range 40% to 70% R.H.
- Air changes (per hr):
Al least 10 complete air changes per hour
- Photoperiod (hrs dark / hrs light):
12 h : 12 h

IN-LIFE DATES:
From: 13 March 1996 to 20 March 1996, sentinel animal: From: 11 March 1996 to 18 March 1996

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): pure test substance

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used
- Concentration (if solution): no vehicle used
- Lot/batch no. (if required): no vehicle used
- Purity: no vehicle used

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

1, 24, 48 and 72h after treatment and on day 8 (one sentinel animal)

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE:
- Washing (if done): Eyewashing phase was not undertaken
- Time after start of exposure: Not applicable

SCORING SYSTEM:
Scoring in accordance to the mentioned guidelines.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein:
An ophthalmoscope or pencil beam torch was used to facilitate inspection of the eyes.

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 3 days

Score:

0.4

Max. score:

2

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: max duration of effects: 72h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 3 days

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: max duration of effects: 24h

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 3 days

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: max duration of effects: 0h

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 3 days

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: max duration of effects: 24h

Irritant / corrosive response data:

Under the conditions of this test, the test item was considered to be non-irritating to the eye.

Other effects:

lnstillation of the test material caused a very slight to slight initial pain response.

Summary-Table of Results: Mean values for ocular lesions (24, 48 and 72 hours after instillation)

Animal number and Sex	Corneal opacity	Iridial lesions	Redness of Conjunctiva	Chemosis
32TD888, Female	0.0	0.0	1.0	0.0
32TD899, Female	0.0	0.0	0.3	0.0
32TD905, Female	0.0	0.0	0.3	0.0
32TD955#, Female	0.0	0.0	0.7	0.0
32TD971, Female	0.0	0.0	0.0	0.0
32TD974, Female	0.0	0.0	0.0	0.0
Overall Mean Score	0.0	0.0	0.4	0.0

#: Sentinel Animal, 72 h assessment undertaken 24 hours late

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No eye irritation was observed. The analogue 'Distillates (Fischer-Tropsch), C8-26 - branched and linear' should also not be classified with regards to eye irritation (Annex VI, EC/67/548 and EC 1272/2008).

Executive summary:

The potential of the test item 'Kerosine (Fischer-Tropsch), limited range, C8-12, branched and linear' (an analogue to 'Distillates (Fischer-Tropsch), full range, C8 -26 - branched and linear') to cause eye irritation on New Zealand White rabbits was investigated according to OECD guideline 405 and US-EPA OTS 798.4500 (Eye irritation). A volume of 0.1 mL test item was applied to six female rabbits.

Under the conditions of this test, the test item was considered to be non-irritating to the eye. Finally, the analogue 'Distillates (Fischer-Tropsch), full range, C8 -26 - branched and linear' should also be 'non-irritating' to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

No skin or eye irritation data are available for GTL Diesel itself. However, data are available for the related substances limited range GTL Kerosine (C8-C12), GTL hydrocarbons C13-C17 (Sarapar 147) and GTL Waxes (C15-C50 and C18 -C50), covering the entire carbon-range of GTL Gasoil. In addition, data are available for a number of other substances in the relevant carbon-range. These are summarised in Tables 1 and 2:

Table 1: Overview of experimental studies on skin irritation

Method	Results	Remarks	Reference
rabbit (New Zealand White) Coverage: semiocclusive (shaved) OECD Guideline 404 (Acute Dermal Irritation / Corrosion)	Not irritating Erythema score: 1 of max. 4 (animal #1) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 7 days) 0.3 of max. 4 (animal #2) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 10 days) 1 of max. 4 (animal #3) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 10 days) 1 of max. 4 (animal #4) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 7 days) 1 of max. 4 (animal #5) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 7 days) 1 of max. 4 (animal #6) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 7 days) Oedema score: 0 of max. 4 (animal #1) (Time point: mean of 24, 48 and 72 hours) (no effects) 1 of max. 4 (animal #2) (Time point: mean of 24, 48 and 72 hours) (fully reversible within: 7 days) 0 of max. 4 (animal #3) (Time point: mean of 24, 48 and 72 hours) (no effects) 0 of max. 4 (animal #4) (Time point: mean of 24, 48 and 72 hours) (no effects) 0 of max. 4 (animal #5) (Time point: mean of 24, 48 and 72 hours) (no effects) 0 of max. 4 (animal #6) (Time point: mean of 24, 48 and 72 hours) (no effects)	2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test material (EC name): Kerosine (Fischer-Tropsch), limited range, C8-12 - branched and linear	Huntingdon Life Sciences, 1997c
rabbit (New Zealand White) OECD Guideline 404 (Acute Dermal Irritation/Corrosion)	Not irritating	2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (Trade name): Sarapar 147 (Fischer-Tropsch hydrocarbons C13-C17)	IIBAT, 2004a
rabbit (New Zealand White) EU Method B.4 (Acute Dermal Irritation/Corrosion)	Not irritating	2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test material (EC name): Paraffin waxes (Fischer-Tropsch), full range C15-C50, branched and linear	SafePharm, 2008a
rabbit (New Zealand White) no guideline stated	Not irritating	2(reliable withrestrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (common name): Alkane 1 (C20 – C24)	Chevron, 1989c
rabbit (New Zealand White) EU Method B.4 (Acute Dermal Irritation/Corrosion)	Not irritating	2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (common name): Alkane 2 (C24)	SafePharm, 1995c
rabbit (New Zealand White) no guideline stated	Not irritating	4 (reliability not assignable) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (common name):Alkanes C14 – C17	IUCLID 2000 dataset for CAS 90622-53-0 citing: HCR Report 84448D/PEQ 3/AC, Sponsor: Petresa
rabbit (New Zealand White) no guideline stated	Not irritating	4 (reliability not assignable) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (common name): Alkane C14	IUCLID 2000 dataset for CAS 90622-53-0 citing: Primary skin irritation (Acceptance No 7056 – 22/9/1987), Sponsor: Enichem Augusta, Ind.

Table 2: Overview of experimental studies on eye irritation

Method	Results	Remarks	Reference
rabbit (New Zealand White) OECD Guideline 405 (Acute Eye Irritation / Corrosion)	Not irritating Cornea score: 0 of max. 4 (mean) (Time point: mean of 24, 48 and 72 hours) (no effects) Iris score: 0 of max. 4 (mean) (Time point: mean of 24, 48 and 72 hours) (fully reversible) (Grade 1 in one animal at one hour post-instillation) Conjunctivae score: 1 of max. 4 (animal #1) (Time point: mean of 24, 48 and 72 hours) (fully reversible) 0.3 of max. 4 (animal #2) (Time point: mean of 24, 48 and 72 hours) (fully reversible) 0.3 of max. 4 (animal #3) (Time point: mean of 24, 48 and 72 hours) (fully reversible) 0.7 of max. 4 (animal #4) (Time point: mean of 24, 48 and 72 hours) (fully reversible) 0 of max. 4 (animal #5) (Time point: mean of 24, 48 and 72 hours) (no effects) 0 of max. 4 (animal #6) (Time point: mean of 24, 48 and 72 hours) (no effects) Chemosis score: 0 of max. 4 (mean) (Time point: mean of 24, 48 and 72 hours) (no effects)	2 (reliable witht restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test material (EC name): Kerosine (Fischer-Tropsch), limited range, C8-12 - branched and linear	Huntingdon Life Sciences, 1997d
rabbit (New Zealand White) OECD Guideline 405 (Acute Eye Irritation / Corrosion)	not irritant	2 (reliable witht restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (Trade name): Sarapar 147 (Fischer-Tropsch hydrocarbons C13-C17)	IIBAT, 2004b
rabbit (New Zealand White) OECD Guideline 405 (Acute Eye Irritation / Corrosion)	not irritant	2 (reliable with restrictions) key study read-across from supporting substance (structural analogue or surrogate) Test material (EC name): Paraffin waxes (Fischer-Tropsch), full range C15-C50, branched and linear	SafePharm, 2008b
rabbit (New Zealand White) OECD Guideline 405 (Acute Eye Irritation / Corrosion)	not irritant	2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (EC name): Distillates (Fischer-Tropsch), heavy, C15-50, branched, cyclic and linear	SafePharm, 2008c
rabbit (New Zealand White) no guideline stated	not irritant	2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (Trade name): Alkane 1 (C20 – C24)	Chevron, 1989d
rabbit (New Zealand White) EU Method B.5 (Acute Eye Irritation/Corrosion)	not irritant	2 (reliable with restrictions) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (Trade name): Alkane 2 (C24)	SafePharm, 1995d
rabbit (New Zealand White) OECD Guideline 405 (Acute Eye Irritation / Corrosion)	not irritant	4 (reliability not assignable) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (common name):Alkanes C14 – C17	IUCLID 2000 dataset for CAS 90622-53-0 citing: HCR Report 84448D/PEQ 3/AC, Sponsor: Petresa
rabbit (New Zealand White) no guideline stated	not irritant	4 (reliability not assignable) supporting study read-across from supporting substance (structural analogue or surrogate) Test material (common name):n-C14 – C16	IUCLID 2000 dataset for CAS 90622-53-0 citing: Scientific Associates, Inc., Vista Chemical Company, 1982

A skin irritation study was conducted with limited range GTL Kerosine (C8-C12) in accordance with OECD 404 and GLP (Huntingdon Life Sciences Ltd, 1997c). 4-hour semi-occlusive application of undiluted test material caused very slight erythema (Grade 1) in all six animals during the first 72 hours after patch removal, persisting in one animal until day 7. Very slight oedema (Grade 1) was apparent in one animal only, during the first 72 hours after patch removal. The observed effects were not sufficient to require classification for skin irritation according to EC criteria.

GLP compliant guideline studies are available for both skin and eye irritation with the substance Sarapar 147, which is a GTL-derived material with carbon range C13-17 (IIBAT, 2004a and 2004b). In the skin irritation study, none of the test animals exhibited any skin reactions at any of the time points observed. In the eye irritation study, no lesions were observed in any of the test animals at the time points observed.

A skin irritation study was conducted with full range GTL Paraffin Waxes (C15-C50) in accordance with OECD 404 and GLP (SafePharm, 2008a). 5-hour semi-occlusive application of undiluted test material caused an isolated incident of mild erythema (Grade 1) at the 48-hour observation. The effects were fully resolved by the 72-hour observation and were not sufficient to require classification for skin irritation according to EC criteria.

These are selected as key studies since the full study reports were available for review, and the test substances were derived from the Fischer-Tropsch process.

An eye irritation study was conducted with limited range GTL Kerosine (C8-C12) in accordance with OECD 405 and GLP (Huntingdon Life Sciences Ltd., 1997d). Instillation of undiluted test material into the rabbit eye produced slight conjunctival redness (Grade 1) in four out of six animals at one and 24 hours after instillation. Iritis (Grade 1) was also apparent in the treated eye of one animal at one hour after exposure. Ocular reactions were present in the remaining two animals. All eyes appeared normal by day 8. The test substance was found to be not irritating to eye. The observed effects were not sufficient to require classification for eye irritation according to EC criteria.

An eye irritation study was conducted with full range GTL Paraffin Waxes (C15-C50) in accordance with OECD 405 and GLP (SafePharm, 2008b). Instillation of undiluted test material into the rabbit eye produced minimal conjunctival irritation (Grade 1) in all treated eyes at the 1 and 48-hour observations. The treated eyes appeared normal at the 24 and 72-hour observations. The test substance was found to be not irritating to eye.

GLP compliant guideline studies are available for both skin and eye irritation with the substance Sarapar 147, which is a GTL-derived material with carbon range C13-17 (IIBAT, 2004a and 2004b). In the skin irritation study, none of the test animals exhibited any skin reactions at any of the time points observed. In the eye irritation study, no lesions were observed in any of the test animals at the time points observed.

The following information is taken into account for any hazard / risk assessment:

The key studies are reliability 1 guideline studies with limited range (C8-C12) GTL Kerosine and full range GTL Paraffin Waxes (C15-C50). The test substances were not irritating to rabbit skin or eyes according to EC criteria. Supporting studies are available for other GTL-derived products covering carbon range C13-C50, which were also non-irritant to rabbit skin and eyes according to EU criteria. Between the key and supporting studies, all carbon numbers present in GTL Gasoil are covered.

Justification for selection of skin irritation / corrosion endpoint:
No skin irritation / corrosion data are available for the substance defined in section 1. For the endpoint conclusion a study of a related substance with a limited range (C8-C12) was selected. Further studies on supporting substances, covering the higher carbon numbers in the range C13-C50, confirm the result (see also Table 1 below "Discussion").

Justification for selection of eye irritation endpoint:
No eye irritation data are available for the substance defined in section 1. For the endpoint conclusion a study of a related substance with a limited range (C8-C12) was selected. Further studies on supporting substances, covering the higher carbon numbers in the range C13-C50, confirm the result (see also Table 2 below "Discussion").

Justification for classification or non-classification

Minimal skin reactions, not sufficient to warrant classification, were observed in some studies.

Substances with higher carbon chain alkanes (paraffins C15-C50 and C18-C50) showed minimal eye irritation, but insufficient to classify according to EU criteria.

Based on skin and eye irritation data for related substances, GTL Diesel is not considered to be corrosive to skin or eyes.

The conclusion of not irritant to the respiratory tract is based on the absence of significant irritating effects on other membranes, specifically the eye.

Although GTL Diesel is not classified, the following additional classification makes sense: R66 (EUH066) Repeated exposure may cause skin dryness or cracking.