Shale oils

Endpoint summary

Description of key information

The median lethal dose of Shale oil after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.
The median lethal dose of Shale oil after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight.

Supporting data

The median lethal dose of Generator oil after 2 hours exposure to white mice, observed over a period of 14 days was 19 mg/L.

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:

12th April - 12th Auguest 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414, Füllinsdorf / Switzerland
- Age at study initiation: 11 - 12 weeks
- Weight at study initiation: 182.3 - 189.6
- Fasting period before study: 17 - 19 hours. Access to water was permitted.
- Housing: in groups of 3 in Makrolon type 4 cages
- Diet (e.g. ad libitum): ad libitum, pelleted diet
- Water (e.g. ad libitum): ad libitum, community tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period

IN-LIFE DATES: From: 12th April 2005 To: 5th May 2005

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
No vehicle used

MAXIMUM DOSE VOLUME APPLIED: 200 mg/kg bw

DOSAGE PREPARATION (if unusual): Homogeneity of the test substance was maintained during administration using a magnetic stirrer.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit dose for classification via the oral route.

Doses:

2000 mg/kg bw (2.04 mL/kg bw)

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing:
Mortality / Viability Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Body weights On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

No statistical analysis performed

Preliminary study:

NDA

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Slightly ruffled fur was observed in all animals of the first-treated group from the 2-hour reading to the 5-hour observation and persisted in one animal up to the examination on test day 2. In the animals from the second-treated group, this symptom was o

Gross pathology:

Congestion of the lungs in one animal. No findings in other animals

Other findings:

NDA

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

The median lethal dose of Shale oil after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight

Executive summary:

In an acute toxic class experiment in accordance with OECD 423 and EU method B.1, performed to GLP standard, 6 female HanRcc:WIST (SPF) rats were given a single 2000 mg/kg bw dose of shale oils middle fraction.

The median lethal dose of Shale oil after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. Study read across from generator oil.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation experiments using mice in 2 hour exposures.

GLP compliance:

no

Limit test:

no

Species:

mouse

Strain:

other: white mice

Sex:

not specified

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

2 h

Concentrations:

See Any other information on materials and methods

No. of animals per sex per dose:

110 animals used in the tests

Control animals:

not specified

Dose descriptor:

LC50

Effect level:

19 mg/L air

Based on:

test mat.

Exp. duration:

2 h

Remarks on result:

other: ± 1.4 mg/L

The influence of volatile compounds of generator oil the activity of the movement and irritation of mucosa was observed already at the concentration of 0.18 - 0.25 mg/l. Increasing the concentration of volatile compounds in the chamber up to 5.9 ml/l the mice looked tired (sluggish) during the test and 30 min after the test. In some cases during the second hour of the test dyspnoea was observed. At higher concentrations (10-12 ml/l) in addition to tiredness and dyspnoea, during the second hour of the test the redness of nose, ears and paws was observed.

Increasing the concentration of the volatile compounds up to 29 ml/l and higher during the second hour of the test additionally to lower movement activity, interruptions in movement coordination and dyspnoea in mice ballisms (mostly of the head and paws) were observed; after 10 , 15 and 20 minutes they lost the ability to stand on their feet (took side position). Afterwards the intoxicative appearance and strengthening of spasms was observed. Before death the convulsions gradually stopped. Animals died when breathing progressively weakened. In few cases death came 2-3 days after the test.

In autopsy of white mice, stagnation phenomenon in brain and lungs were observed. Quite often macroscopic signs of degenerative changes in liver were observed.

First signs of intoxication with volatile compounds of generator oil in white mice were observed at concentrations of 0,25 mg/l. The main parameters of toxicity to white mice were as follows: LC0 = 13 mg/l, LC100 = 30 mg/l, LC50 = 19 ± 1.4 mg/l.

As described before we can see that intoxication with volatile compound of generator oil are characterized with the same symptoms as of intoxication with other substances. These kind of symptoms as change in the character of breathing, disorder of movement coordination, cramps, lying on the side etc. are also signs of intoxication with organic solvents; redness of nose, ears and paws are observed in case of intoxication with toluene; head and paw cramps indicate impact of phenols etc.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

The LC50 of generator oil to white mice was 19 ± 1.4 mg/L.

Executive summary:

White mice were exposed to generator oil in an aerosol inhalation experiment for 2 hours.

The LC50 of generator oil to white mice was 19 ± 1.4 mg/L.

Endpoint conclusion

Dose descriptor:

LC50

Value:

19 000 mg/m³ air

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:

8th April - 12th August 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks. Female: 12 weeks
- Weight at study initiation: NDA
- Fasting period before study: NDA
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard provided ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 8th - 12th April 2005

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 5
- Humidity: 30 - 70 %
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark with music played during the daytime period

IN-LIFE DATES: From: 8th April 2005 To: 27th April 2005

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: NDA
- % coverage: 10 %
- Type of wrap if used: The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin flushed with luke warm water
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.04 mL/kg bw
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A

VEHICLE
N/A

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 per sex per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, local signs

Statistics:

No statistical analysis used.

Preliminary study:

not applicable.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No systemic signs of toxicity were observed during the course of the study. Due to brown discoloration of the application site in all animals, local symptoms could not be assessed on test day 2. Slight general erythema was observed in six animals at the r

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

NDA

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

The median lethal dose of Shale oil after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight.

Executive summary:

Five male and five female HanRcc:WIST (SPF) rats were treated with Shale oil at 2000 mg/kg by dermal application in accordance with OECD 402 and to GLP standard. The test item was applied undiluted as delivered from the sponsor at a volume dosage of 2.04 mL/kg. The application period was 24 hours.

No mortality, clinical signs or abnormal body weight changes were observed. Mild to moderate skin irritation effects were observed in all animals.

The median lethal dose of Shale oil after single dermal administration to rats of both sexes, observed over a period of 14 days is:

LD50 (rat): greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute toxicity: oral

In an acute toxic class experiment in accordance with OECD 423 and EU method B.1, performed to GLP, 6 female HanRcc:WIST (SPF) rats were given a single 2000 mg/kg bw dose of shale oils middle fraction.

The median lethal dose of Shale oil after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight

Acute toxicity: dermal

Five male and five female HanRcc:WIST (SPF) rats were treated with Shale oil at 2000 mg/kg by dermal application in accordance with OECD 402 and to GLP standard. The test item was applied undiluted as delivered from the sponsor at a volume dosage of 2.04 mL/kg. The application period was 24 hours.

No mortality, clinical signs or abnormal body weight changes were observed. Mild to moderate skin irritation effects were observed in all animals.

The median lethal dose of Shale oil after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight.

Acute toxicity: inhalation

In accordance with column 2 of REACH Annex VIII, in addition to the oral route (Annex VII, 8.5.1.), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. Taking account of the substance uses, exposure via inhalation is unlikely. Furthermore, data are available via the dermal route as a second route of exposure. Testing via the inhalation route of exposure is therefore not considered to be required. Acute inhalation toxicity data on generator oil are provided as supporting information only.

Supporting data:

White mice were exposed to generator oil in an aerosol inhalation experiment for 2 hours.

The LC50 of generator oil to white mice was 19 ± 1.4 mg/L.

Justification for classification or non-classification

Based upon the high LD50 values for oral, inhalation and dermal exposure, and the absence of other major significant effects, the available study data indicates that shale oils middle fraction does not need to be classified for acute toxicity according to Regulation (EC) No 1272/2008. However, to take account of the potential variability in the composition of the UVCB starting material, and the potential variation in the composition of the UVCB substance in scope of this registration, the worst case classification of H301 (Toxic if swallowed), H311 (Toxic in contact with skin), H332 (Harmful if inhaled) and H304 (May be fatal if swallowed and enters airways) is applied.

For further information, please refer to the document 'Shale oils RAAF Report' as included in section 13.