Naphtha (Fischer-Tropsch), light, C4-10-branched and linear

Endpoint summary

Description of key information

- Acute toxicity (oral): study 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 toxicity (inhalation): study on supporting substance with limited range (C7-C10) conducted according to OECD 403 and GLP, reported an acute inhalation median lethal concentration (4 hour LC50) in the rat > 5040 mg/m³ air (analytical).

- Acute toxicity (dermal): study on supporting substance with limited range (C7-C10) conducted according to OECD 403 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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% ofthe 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.
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
- Lot/batch no. (if required):
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 (or other?):
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, other:
yes

Statistics:

No statistical procedures were required.

Preliminary study:

no clinical signs of toxicity

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

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	207	235	268	28	33
5000	Female 2 -0	202	236	259	34	23
5000	Female 2 -1	206	239	263	33	24
5000	Female 2 -2	203	230	260	27	30
5000	Female 2 -3	211	238	253	27	15

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of 'Naphtha (Fischer-Tropsch), light, C4-10 - branched and linear' in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight --> the test material is of low toxicity via the oral route; using EU GHS, it is unclassified.

Executive summary:

An acute oral toxicity study with rats was performed according to OECD Guideline 420 (Fixed-dose method; adopted 2001) and Method B.1 of Commission Directive 2004/73/EC.

- Mortality: no deaths

- Clinical observations: no signs of systemic toxicity

- Body Weight: within expected gains

- Necropsy: no abnormalities

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 study is GLP compliant and has Klimisch score 1.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

(see "Principles of method if other than guideline")

GLP compliance:

yes

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
- Weight at study initiation: males: 278,4 - 310,1g; females: 214,2 - 229,1g
- Fasting period before study: no
- Housing: individually in hanging stainless steel wire mesh cages
- Diet (e.g. ad libitum): Purina Certified Laboratory Chow 5002®, ad libitum
- Water (e.g. ad libitum): Tap, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71-74
- Humidity (%): 44-56
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle, artificial light

IN-LIFE DATES:
- Males: from 23 April, 1986 to 26 June, 1986 (date of exposure)
- Females: from 20 April, 1986 to 26 June, 1986 (date of exposure)

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: none

Details on inhalation exposure:

Chamber Operations and Test Substance Administration:
Exposure of the test animals was conducted in a 250 liter stainless steel and glass chamber. The chamber is constructed with a square cross-sectioned area and pyramidal top and base. It was operated in a dynamic mode, with total airflow through the chamber of 2.2 cubic feet per minute (cfm) as measured by a calibrated orifice gauge.
Test material was used as received and was generated as a vapor in the breathing zone of the animals. NAPHTHA (PETROLEUM), LIGHT ALKYLATE was introduced at a rate of 0.34 to 0.51 ml/minute into the top of a vertical counter current heated column. The column was packed with Propac steel mesh and heated by circulation of water from a heated waterbath (74 to 75°C) around the steel mesh. Prewarmed nitrogen gas was introduced at the bottom of the column at a rate of 5.5 to 6.0 liters per minute (1pm). The nitrogen and the NAPHTHA (PETROLEUM), LIGHT ALKYLATE vapours were then mixed with diluting air and introduced into the exposure chamber. Following four hours of exposure, the test material generation system was turned off. Subsequently, air was drawn through the exposure chamber for an additional half-hour period to clear the NAPHTHA (PETROLEUM), LIGHT ALKYLATE vapours. Afterwards, the chamber was opened and the animals were removed.

Atmospheric Sampling:
The exposure chamber atmosphere was recirculated (undiluted) through a Miran 980 infrared (IR) analyzer. Commencing at five minutes after the start of test material generation and at intervals of five to fifteen minutes thereafter, the test atmosphere was analyzed by its IR absorption at 3.393 microns. The atmospheric concentration of NAPHTHA (PETROLEUM), LIGHT ALKYLATE was determined by comparison of absorbance with a standard curve which was prepared with known concentrations of NAPHTHA (PETROLEUM), LIGHT ALKYLATE.
Chamber temperature and relative humidity were monitored continuously during the exposure. Readings were recorded at one-hour intervals. During each hour of the exposure, the test atmosphere was also analyzed gravimetrically and visually (by flashlight) for the presence of any NAPHTHA (PETROLEUM), LIGHT ALKYLATE aerosol. Gravimetric measurement of the test material aerosol concentration was accomplished by drawing a calibrated volume of test atmosphere through a preweighed 25 mm Gelman glass fiber (Type A/E) filter. The aerosol concentration, if any, in the drawn volume was determined by dividing the difference in filter weight by the sample volume.
Appropriate components of the generation system and test material container were weighed before and after the exposure to determine the quantity of test material consumed. This quantity, when divided by the total airflow through the chamber, yielded the nominal exposure concentration.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

analytical: 5040 mg/m³

No. of animals per sex per dose:

5 male and 5 female/dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations every 15 minutes during the first hour of exposure, hourly thereafter until completion of exposure. Post-Exposure (Test Days 2-15): for mortality twice daily; detailed physical examination daily. Weighing: One pretest and on Test Days 8 and 15 (Post-exposure days 7 and 14).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 040 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths resulted.

Clinical signs:

other: Clinical signs were languid behaviour and hunched appearance.

Body weight:

No treatment-related effects.

Gross pathology:

No treatment-related effects.

Other findings:

Histopathology (lungs only): histopathology evaluation of the lung were considered unremarkable in that no treatment related effects were apparent.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the conditions of this study, the LC50 for acute inhalation exposure to 'Naphtha (petroleum), light alkylate' is > 5040 mg/m³.

Executive summary:

'Naphtha (petroleum), light alkylate' was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats at the analytical vapour concentration of 5040 mg/m³ to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure. There were no mortality and the clinical signs observed were languid behaviour and hunched appearance. There were no treatment-related effects observed at necropsy.

Based on the conditions of this study, the LC50 for acute inhalation exposure to 'Naphtha (petroleum), light alkylate' is > 5040 mg/m³.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

The study is GLP compliant and has Klimisch score 2 (due to read-across approach).

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09/84 - 10/84

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

The test material 'Naphtha (petroleum), light alkylate' is a closely related substance to 'Naphtha (Fischer-Tropsch), light, C4-10 branched and linear'.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

see below "Principles of method if other than guideline"

Principles of method if other than guideline:

During the study period the relative humidity of the animal room ranged from 60 to 78%. The guideline specified the relative humidity as 30-70%. This deviation is not considered to have had an effect on the validity of this study.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2717-3136 g
- Fasting period before study: no data
- Housing: screen-bottom cages
- Diet (e.g. ad libitum): ad libitum (Purina Certified Rabbit Chow f5322)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 14d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%): 60-78%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: September 26, 1984 To: October 10, 1984

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: eight-ply gauze bandage and overwrapped with Saran Wrap and Elastoplast tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed, but wiped clean with wet disposable towels
- Time after start of exposure: 24 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.434 - 6.272 g
- Concentration (if solution): 100% (w/w)
- Constant volume: no

Duration of exposure:

24 hrs

Doses:

single dosage level of 2.0 g/kg bw

No. of animals per sex per dose:

4 male and 4 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rabbits were observed for clinical signs and mortality hourly for the first 6 hours after dosing, then
daily for dermal irritation and twice daily for clinical signs and mortality for a period of 14 days. Body weights were taken just prior to administration, at 7 days, and at study termination.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, gross necropsy

Statistics:

none

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no deaths

Clinical signs:

other: With the exception of dermal irritation, no clinical signs were observed during the study period. A pain response (vocalization) was elicited from all of the animals following application of the test material. Dermal irritation observed during the study r

Gross pathology:

4 male rabbits:
- one animal --> no visible lesions
- one animal --> skin of test site thickened
- two animals --> skin of test site slightly thickened;

4 female rabbits:
- one animal --> skin of test site thickened
- three animals --> no visible lesions

Other findings:

none

Summary of body weights and mortality:

Sex	Dosage Level [g/kg bw]	Average Body Weights (g) Initial Day 7 Terminal			Mortality (number dead / number dosed)
Male	2.0 (Intact)	2.830	2.923	3.140	0/2
Male	2.0 (Abraded)	2.870	2.984	3.232	0/2
Female	2.0 (Intact)	2.829	2.911	3.115	0/2
Female	2.0 (Abraded)	2.931	3.062	3.352	0/2

Summary of clinical signs (number of animals affected - dose level 2000 mg/kg bw):

	Hours						Days
	1	2	3	4	5	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Males: appeared normal	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4
Females: appeared normal	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material Naphtha (petroleum), light alkylate (EC 265-068-8) in the male and female New Zealand White strain rabbit was estimated to be greater than 2000 mg/kg bodyweight.

Executive summary:

An acute dermal toxicity study with rabbits was performed similar to OECD Guideline 402:

- Mortality: no deaths

- Clinical observations: no signs of systemic toxicity

- Body Weight: within expected gains

- Necropsy: no visible lesions [four of eight animals]; skin of test site (slightly) thickened [four of eight animals]

The acute dermal median lethal dose (LD50) of the test material Naphtha (petroleum), light alkylate in the male and female New Zealand White strain rabbit was estimated to be greater than 2000 mg/kg bodyweight.

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).

Additional information

Oral

‘Naphtha (Fischer-Tropsch), light, C4-C10 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.

 

Inhalation

There are no data available on the acute toxicity of ‘Naphtha (Fischer-Tropsch), light, C4-C10 branched and linear’ upon inhalation exposure. However, astudy was performed to assess the acute inhalation toxicityof the closely related substance ‘Naphtha (petroleum), light alkylate’ (covering the carbon numbers in the range C7-C10), whereat the used method was compatible withOECD403. It was considered that the acute inhalation median lethal concentration (4 hour LC50) of the test material in the rat, was > 5040 mg/m3. There was no mortality and the clinical signs observed were languid behaviour and hunched appearance. There were no treatment-related effects observed at necropsy.  

Dermal

There is no data available on the acute dermal toxicity of ‘Naphtha (Fischer-Tropsch), light, C4-C10 branched and linear’. However, a study on the acute dermal toxicity of the related substance ‘Naphtha (petroleum), light alkylate’ (with a limited range of C7-C10) reported a LD50 value of > 2000 mg/kg bw for the test substance in rats. There were no deaths, no systemic toxicity or treatment related abnormalities at necropsy reported for the test substance.

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 – inhalation endpoint

No acute toxicity data (via inhalation route) are available for the substance defined in section 1. For the endpoint conclusion a study of a related substance with a limited range, (C7-C10) was selected.

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, (C7-C10) was selected.

Justification for classification or non-classification

On the basis of the available data, ‘Naphtha (Fischer-Tropsch), light, C4-C10 branched and linear’ does not require classification for lethal effects following a single exposure according to Regulation 1272/2008/EC.

The self classification STOT Single Exp. 3; H336’ is based on the classification of the constituent n-hexane (presence of n-hexane in the test material up to 20%). Moreover the UVCB substance contains further hydrocarbons/constituents, which are also classified as STOT Single Exp. 3; H336' (e.g. 2 -methylbutane; n-pentane; 2 -methylpentane; 2 -methylhexane; n-heptane; 2,2,4 -trimethylpentane).

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 Aspiration Toxicity Category 1 (according to Regulation 1272/2008/EC).