[No public or meaningful name is available]

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2014-02-04 to 2014-03-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

2009

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

C21-C50 branched, cyclic and linear saturated hydrocarbons - Distillates

IUPAC Name:

C21-C50 branched, cyclic and linear saturated hydrocarbons - Distillates

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

other: RccHan: WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 200 - 350 g
- Fasting period before study:
- Housing: groups of 3 by sex in solid-floor polypropylene cages
- Diet: Harlan 2014C Rodent Diet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70 %
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: The cylindrical exposure chamber had a volume of approximately 30 litres.

- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere.

- Source and rate of air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the nebulizer. The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump.

- Method of conditioning air: Infusion pump

- System of generating particulates/aerosols: The test item was aerosolized using a glass concentric jet nebulizer located at the top of the exposure chamber. The nebulizer was connected to a plastic syringe attached to an infusion pump, which provided a continuous supply of test item under pressure, and to a metered compressed air. Oxygen levels within the exposure chamber were measured by an electronic oxygen analyser. The test atmosphere was generated to contain at least 19 % oxygen.

- Method of particle size determination: The particle size was determined 3 times during the exposure period using a Marple Personal Cascade Impactor. It consisted of 6 impactor stages (8.9, 6.2, 3.6, 1.6, 0.93 and 0.37 µm cut points) with stainless steel collection substrates and a backup glass fibre filter, housed in an aluminium sampler. The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. The proportion of aerosol (%) less than 8.9, 6.2, 3.6, 1.6, 0.93 and 0.37 µm was calculated. The resulting values were converted to probits and plotted against Log10 cut-point size. From this plot the MMAD was determined (as the 50 % point) and the geometric standard deviation was calculated.

- Treatment of exhaust air: The extract from the exposure chamber passed through a trap and was connected to a high efficiency filter to a metered exhaust system.

- Temperature, humidity, pressure in air chamber: Prior to the start of the test, test item atmospheres were generated within the exposure chamber. During the characterisation period test item input rates were varied to achieve the required atmospheric concentration whilst maintaining a slightly negative pressure. The temperature (19 -20 °C) and relative humidity (14 - 22 % ) inside the exposure chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animals' breathing zone of the chamber and recorded every 30 min throughout the 4-hour exposure period.

TEST ATMOSPHERE
- Brief description of analytical method used: Homogeneity of the test atmosphere within the chamber was not determined during the study. Filter samples were used for chemical analysis to determine whether the composition of the test item was similar to the composition of the airborne test material. Prior to the inhalation phase, the non-volatile component of the test item was determined by adding a small, known amount of the test item to glass fibre filters and recording their weights. The filters were then dried in a desiccator between 19 and 22 °C for approximately 24 hours and then weighed again. The difference in the two weights was the volatile content and the non-volatile component was calculated as a percentage. The mean non-volatile component was found to be 99.92 %.

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Predicted amount under 4 µm = 88.6%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD 122 um / GSD 2.69

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.0 mg/L (target concentration). The mean achieved concentration was 102 % of target, 5.12 mg/L.

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights were recorded on the arrival of the animals, prior to the treatment, and on days 1, 3, 7 and 14. Animals were observed for clinical signs prior to the treatment, 1 hour after the treatment, and once a day for 14 days.
- Necropsy of survivors performed: yes; at necropsy, internal and external examination was performed, where the respiratory tract was subject to detailed examination.
- Other examinations performed: clinical signs of toxicity were noted during the study period.

Statistics:

Standard deviation was calculated for the mean concentration achieved. The mortality data was used to derive an estimate of the acute inhalation median lethal concentration (LC50) of the test item.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.12 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: (aerosol)

Mortality:

No mortality noted during the 14-day study period.

Clinical signs:

other: Increased respiratory rate was noted during exposure. On removal from the chamber, there were frequent instances of increased respiratory rate. Occasional instances of ataxia, tip-toe gait, and laboured respiration were also apparent. One hour after remov

Body weight:

All males and one female exhibited slight body weight losses on the first day post exposure. All male rats exhibited body weight gains during the recovery period. One female animal exhibited slight weight loss from day 1 till day 3 post-exposure and another female animal exhibited no body weight gain during the final week of the study.

Gross pathology:

No macroscopic abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

other: EU-GHS criteria not met

Conclusions:

LC50 > 5.12 mg/L air for a cut of GTL base oil (linear, branched and cyclic alkanes, covering the carbon range from C21 to C50, with a viscosity of ~18mm2/s at 40 °C and ~4mm2/s at 100 °C)

Executive summary:

An acute inhalation toxicity study for a cut of GTL base oil (linear, branched and cyclic alkanes, covering the carbon range from C21 to C50, with a viscosity of ~18mm2/s at 40 °C and ~4mm2/s at 100 °C) was performed on 3 male and 3 female rats. Only the nose of each animal was exposed to the aerosolised test material for 4 hours. Observations for clinical signs and body weight changes were carried out regularly during the 14 -day study period. Necropsy was performed at the end of the study period. All animals were subject to detailed internal and external examinations, and any macroscopic changes were recorded.

Prior to the day of exposure each rat was acclimatised for approximately 2 hours. On the day of exposure, each rat was held individually in a tapered polycarbonate restraining tube fited onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere.

The test item was aerosolised using a glass concentric jet nebulizer. The cylindrical exposure chamber had a volume of 30 litres. Homogeneity of the test atmosphere within the chamber was not specifically determined during the study. During the characterization period test item input rates were varied to achieve the required atmospheric concentrations whilst maintaining a slightly negative pressure. The nominal concentration was 266 % of the actual mean achieved atmosphere concentration and shows that keeping the aerosol airborne was relatively straightforward. The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor.

The mean achieved atmosphere concentration was 5.12 mg/L. The Mean Mass Median Aerodynamic Diameter was 1.22 µm, Inhalation fraction was 88.6 % < 4 µm and Geometric Standard Deviation was 2.69. There was no mortality during the 14 -day study period. Increased respiratory rate was noted during exposure. On removal from the chamber, there were frequent instances of increased respiratory rate. Occasional instances of ataxia, tip-toe gait, and laboured respiration were also apparent. One hour after removal slight improvement in the condition of the animals was observed. One day after exposure all animals exhibited increased respiratory rate, hunched posture and pilo-erection. Animals appeared normal by days 9-10 of the 14-day study period. All males and one female exhibited slight body weight losses on the first day post exposure. All male rats exhibited body weight gains during the recovery period. One female animal exhibited slight weight loss from day 1 till day 3 post-exposure and another female animal exhibited no body weight gain during the final week of the study.

No macroscopic abnormalities were noted at necropsy.

An LC50 value greater than 5.12 mg/L air was concluded. The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.