C8-C26 branched and linear hydrocarbons – Distillates

Endpoint summary

Description of key information

- Acute oral toxicity study (SafePharm, 2006a), conducted according to OECD 420 (Acute Oral Toxicity - Fixed Dose Method) and GLP, reported a LD50 in male and female rats >5000 mg/kg bw.
- Acute dermal toxicity study (Huntingdon Life Sciences, 1997b), conducted on related substance with limited range (C8-C12), according to OECD 402 (Acute Dermal Toxicity) and GLP, reported an LD50 in male and female rats >2000 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-10-03 to 2006-10-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-study according to relevant guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.
- Weight at study initiation: The bodyweights fell within an interval of i 20% of the initial bodyweight of the first treated animal.
- Fasting period before study: With the exception of an overnight fast immediately before dosing and for approximately three to four hours after
dosing, free access to mains drinking water and food (Certified Rat and Mouse Diet (Code SLF2) was allowed throughout the study.
- Housing: On receipt the animals were randomly allocated to cages.
- Diet (e.g. ad libitum): Overnight fast immediately before dosing and for approximately three to four hours after dosing (free access to mains
drinking water and food was allowed throughout the study).
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was set to achieve limits of 19 to 25°C.
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70%.
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not applicable
- Amount of vehicle (if gavage): Not applicable
- Justification for choice of vehicle: Not applicable
- Purity: Not applicable

MAXIMUM DOSE VOLUME APPLIED:
5000 mg/kg

DOSAGE PREPARATION (if unusual):
Not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not applicable

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology: yes

Statistics:

No statistical procedures were applied.

Preliminary study:

Following a preliminary test in which there were no deaths at a dose level of 5000 mg/kg, an additional 4 fasted Sprague-Dawley DC rats received a dose of 5000 mg of the undiluted test material per kg body weight by gavage.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

- Mortality: no deaths

Clinical signs:

other: - Clinical observations: no signs of systemic toxicity

Gross pathology:

- Necropsy: no abnormalities

Other findings:

None

Table 1: Individual Clinical Observations and Mortality Data

Dose level	Animal	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
(mg/kg)	No.	0,5	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
5000	Female 1 -0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5000	Female 2 -0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5000	Female 2 -1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5000	Female 2 -2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
5000	Female 2 -3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0- No signs of systemic toxicity

Table 2: Individual Body weights and Bodyweight changes

Dose level	Animal	Bodyweight at day (g)			Body weight gain during week (g)
(mg/kg)	No.	Day 0	Day 7	Day 14	Day 1	Day 7
5000	Female 1 -0	213	247	268	34	21
5000	Female 2 -0	190	213	216	23	3
5000	Female 2 -1	216	251	273	35	22
5000	Female 2 -2	198	236	249	36	15
5000	Female 2 -3	206	229	238	23	9

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: other: Since the substance is composed of aliphatic hydrocarbons and has low viscosity, it may present an aspiration hazard in humans following oral exposure. It is therefore appropriate to classify the substance as ‘Harmful: may cause lung damage if swallowed’.

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight. Using the EU Globally Harmonised System (GHS), it would be ‘unclassified’. However, since the substance is composed of aliphatic
hydrocarbons and has low viscosity, it may present an aspiration hazard in humans following oral exposure. It is therefore appropriate to classify
the substance as ‘Harmful: may cause lung damage if swallowed’.

Executive summary:

'Distillates (Fischer-Tropsch), C8-26 branched and linear' was tested in an acute oral toxicity study according to the fixed dose method (OECD 420). Following a preliminary test in which there were no deaths at a dose level of 5000 mg/kg, an additional 4 fasted Sprague-Dawley DC rats received a dose of 5000 mg of the undiluted test material per kg body weight by gavage. There were no signs of toxicity, all animals showed normal gains in body weight, and there were no abnormalities on necropsy. The acute oral median lethal dose (LD₅₀) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The selected study is GLP compliant and has Klimisch score 1. Further reliable study on supporting substance with limited range (C8-16) confirms the result.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

02/1996 - 11/1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: male animals were approximately 7 - 8 weeks, the females approximately 10 - 11 weeks old
- Weight at study initiation: 208 - 240 g for males and 212 - 232 g for females
- Fasting period before study: none
- Housing: stainless steel grid cages; on completion of dosing, the animals were accommodated in individual cages
- Diet (e.g. ad libitum): ad libitum [pelleted rodent diet (RM1 (E)]
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23.5
- Humidity (%): 46-52
- Air changes (per hr): at least 10 complete air changes per hour without recirculation
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: approximately December 1995 (female)/ January 1996 (male) To: 07 March 1996

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: body surface area
- % coverage: 5 cm x 5 cm area (approximately 10% of the body surface area)
- Type of wrap if used: 5 cm x 5 cm gauze patch, occluded with aluminium foil; the foil was kept in place and protected by a pad of cotton wool and a bandage of waterproof plaster and tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dermal site was gently wiped with wet disposable tissues to remove residual test material
- Time after start of exposure: 24 hours after administration


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not available - quantity of dose was determined for each animal according to its bodyweight
- Constant volume used: no


VEHICLE
none

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- observations: three separate recordings of signs were made during the first hour after administration and two further recordings during the
remainder of Day 1; from Day 2 onwards, the animals were inspected twice daily and recordings of systemic and local signs were made once daily
- weighing: on days 1, 8 and 15
- Necropsy of survivors performed: yes

Statistics:

none

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no death

Clinical signs:

other: no local or systemic sign of reaction to treatment

Gross pathology:

necropsy revealed no significant macroscopic lesion

Other findings:

none

1) Bodyweights(Dosage 2000mg/kg bw):

	Bodyweight [g]
	Male-1	Male-2	Male-3	Male-4	Male-5
Day -1	227	226	208	240	239
Day 1	232	238	214	246	248
Day 8	259	278	227	285	281
Day 15	296	331	264	337	323
Increment	69	105	56	97	84
Mean of Increment					82

	Bodyweight [g]
	Female-1	Female-2	Female-3	Female-4	Female-5
Day -1	232	217	212	221	231
Day 1	237	221	215	225	234
Day 8	252	238	244	235	244
Day 15	265	253	237	255	280
Increment	33	36	25	34	49
Mean of Increment					35

2) Necropsy observations(Dosage 2000 mg/kg bw):

Animal and sex	Died or Sacrificed	Time of death	Necropsy observations
Male-1	Sacrificed	Day 15	External Application site: No significant lesion Other: No significant lesion Internal No significant lesion
Male-2	Sacrificed	Day 15
Male-3	Sacrificed	Day 15
Male-4	Sacrificed	Day 15
Male-5	Sacrificed	Day 15
Female-1	Sacrificed	Day 15	External Application site: No significant lesion Other: No significant lesion Internal No significant lesion
Female-2	Sacrificed	Day 15
Female-3	Sacrificed	Day 15
Female-4	Sacrificed	Day 15
Female-5	Sacrificed	Day 15

3) Systemic and local signs (Dosage 2000 mg/kg bw):

	Number of animals showing signs+
	Male	Female
No abnormality detected	5	5
Total number of survivors	5	5

+ Five animals in each sex-group

4) Mortality (Dosage 2000 mg/kg bw):

	Mortality
	Male	Female	Combined
Dosage 2000 mg/kg bw	0/5	0/5	0/10

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

There was no death and no local or systemic sign of reaction to treatment. All animals achieved anticipated bodyweight gains and necropsy revealed
no significant macroscopic lesion. Under the conditions of this study, the acute dermal median lethal dosage (LD50) of the test material 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' was greater than 2000 mg/kg. According to Annex VI of Council Directive 67/548/EEC 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' should be unclassified with regards to acute dermal toxicity. Using the EU Globally Harmonised System (GHS), it would be also ‘unclassified’. Finally, the analogue 'Distillates (Fischer-Tropsch), C8-26-branched and linear' also should not be classified.

Executive summary:

According to EU-Method B.3 the acute dermal toxicity of 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear'

, a structural analogue to 'Distillates (Fischer-Tropsch), C8 -26 - branched and linear`, was investigated in a group of five male and five female CD rats. The test material was applied to the closely-clipped dorsum of each animal at a dosage of 2000 mg/kg bodyweight, and was covered by an occlusive dressing for 24 hours.

Mortality, systemic and local signs of reaction to treatment were recorded during a subsequent 14-day period of observation. The animals were killed on the following day and subjected to necropsy.

There was no death and no local or systemic sign of reaction to treatment. All animals achieved anticipated bodyweight gains and necropsy revealed no significant macroscopic lesion. Under the conditions of this study, the acute dermal median lethal dosage (LD50) of the test material was greater than 2000 mg/kg bw. Finally, the acute dermal median lethal dosage (LD50) of the structural analogue 'Distillates (Fischer-Tropsch), C8 -26 - branched and linear` also should be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and has Klimisch score 2 (due to read-across approach).
In addition, relevant acute dermal toxicity studies with rats and rabbits are available for a number of related substances following administration by the dermal route, covering the higher carbon numbers in the range C12-C24. The full study reports were not available for review, however, in all cases, the reported LD50 values are >2000 mg/kg bw (see Table below "Discussion").

Additional information

GTL Gasoil was tested in an acute oral toxicity study according to the fixed dose method (OECD 420). Following a preliminary test in which there were no deaths at a dose level of 5000 mg/kg, an additional 4 fasted Sprague-Dawley DC rats received a dose of 5000 mg of the undiluted test material per kg body weight by gavage. There were no signs of toxicity, all animals showed normal gains in body weight, and there were no abnormalities on necropsy (SafePharm 2006a).

In addition, relevant data are available for a number of related substances following administration by the dermal and inhalation route.

No acute dermal toxicity data are available for GTL Gasoil. A study on the acute dermal toxicity of the related substance GTL Kerosine with a limited range, (C8-C12) reported an LD₅₀value of >2000 mg/kg bw for the test substance in rats (Huntingdon Life Sciences, 1997b). There were no deaths, no systemic toxicity or treatment related abnormalities at necropsy reported for the test substance.

In addition, relevant acute dermal toxicity studies with rats and rabbits are available for a number of related substances following administration by the dermal route, covering the higher carbon numbers in the range C12-C24. In all cases, the reported LD₅₀values are >2000 mg/kg bw (see Table 5.2.2).

Taking all available acute dermal toxicity data for relevant carbon numbers into consideration it can be concluded that the LD₅₀for GTL Gasoil (C8-C26) is >2000 mg/kg bw. The key study was selected as Huntingdon Life Sciences, 1997b, since the full study report was available for review and the test substance was derived from the Fischer-Tropsch process.

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

The key acute oral toxicity study (SafePharm, 2006a), conducted according to OECD 420 (Acute Oral Toxicity - Fixed Dose Method) and GLP, reported an LD₅₀in male and female rats >5000 mg/kg bw.

The key acute dermal toxicity study (Huntingdon Life Sciences, 1997b), conducted according to OECD 402 (Acute Dermal Toxicity) and GLP, reported an LD₅₀in male and female rats >2000 mg/kg bw.

Value used for CSA:

- LD₅₀(oral): >5000 mg/kg bw

- LD₅₀(dermal): >2000 mg/kg/ bw.

The results of experimental studies are summarised in the following table (whereby only a few full study reports were available for review):

Table: Summary of relevant acute toxicity data

Substance	Test method	Result LD50(mg/kg) or LC50(mg/m^3)	Comments	Reference (please see also attached CSR)
Oral exposure
Distillates (Fischer-Tropsch), C8-26-branched, cyclic and linear	OECD 420	>5000 (rat)	GLP	SafePharm, 2006a
Limited range kerosine (C8 – C12)	Annex V	>5000 (rat)	GLP	HLS, 1996a
Alkane 1 (C20 – C24)	Not stated	>5000 (rat)	GLP	Chevron, 1989a
Alkane 2 (C24)	Annex V	>5000 (rat)	GLP	SafePharm, 1995a
n-C14 – C16	-	>5250 (rat)	Non-GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: Scientific Associates, Inc., Vista Chemical Company, 1982a
n-C10 – C12	-	>3990 (rat)	Non-GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: Scientific Associates, Inc., Vista Chemical Company, 1975
C14 – C17	OECD 401	>5000 (rat)		IUCLID 2000 dataset for CAS 90622-53-0 citing: HCR Report 84448D/PEQ 1/AC, Sponsor: Petresa
Alkane C14	Annex V	>5000 (rat)	Non-GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: Acute oral toxicity (Acceptance No 7056 – 22/9/1987), Sponsor:,
Dermal exposure
Limited range kerosine (C8 – C12)	Annex V	>2000 (rat)	GLP	HLS, 1996b
Alkane 1 (C20 – C24)	Not stated	>2000 (rat)	GLP	Chevron, 1989b
Alkane 2 (C24)	Annex V	>2000 (rat)	GLP	SafePharm, 1995c
Alkane C14	OECD 402	>2000 (rat)	GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: HCR Report 84448D/PEQ 2/AC, Sponsor: Petresa
n-C10 – C12	-	3980 – 5730 (rabbit)	Non-GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: Scientific Associates, Inc., Vista Chemical Company, 1982b

n-C12 – C14	-	>2000 (rabbit)	Non-GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: Scientific Associates, Inc., Vista Chemical Company, 1982c
n-C14 – C16	-	>2000 (rabbit)	Non-GLP	IUCLID 2000 dataset for CAS 90622-53-0 citing: Scientific Associates, Inc., Vista Chemical Company, 1982d

Justification for selection of acute toxicity – oral endpoint
Only one study available with the identify of test material same as for substance defined in section 1.

Justification for selection of acute toxicity – dermal endpoint
No acute dermal toxicity data are available for the substance defined in section 1. For the endpoint conclusion a study on the acute dermal toxicity 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 C12-C24, confirm the result.

Justification for classification or non-classification

On the basis of the available data, GTL Diesel does not require classification for lethal effects following a single exposure according to Regulation 1272/2008/EC.

Since the substance is composed of aliphatic hydrocarbons and has low viscosity (2 – 4.5 cSt at 40°C), it may present an aspiration hazard in humans following oral exposure. It is therefore appropriate to classify the substance as Aspiration Toxicity Category 1 according to Regulation 1272/2008/EC.