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Administrative data

Description of key information

1) Acute oral toxicity: The acute oral median lethal dose (LD50) of the test material 'Paraffin waxes (Fischer-Tropsch), full range, C15-50 - branched and linear' in the female Sprague-Dawley CD strain rat was estimated to be greater than 5000 mg/kg bodyweight.

2) Acute inhalation and dermal toxicity: Based on lack of skin irritation and systemic effects in a skin irritation study the substance is not considered to acute harmful in contact with skin. Moreover, the substance is unlikely to form aerosols or particles of inhalable size. Therefore it is considered justifiable not to conduct these studies.

Supporting data on related substances (covering the range, C18-50) indicate the low dermal and inhalation toxicity:

a) Acute inhalation toxicity study (Harlan, 2014), conducted according to OECD 436 and GLP, reported an acute inhalation median lethal concentration (4 hr LC50) 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), in the RccHanTM: WIST strain rat >5 mg/L.

b) Acute dermal toxicity study (Harlan, 2015), conducted according to OECD 402 (Acute Dermal Toxicity) and GLP, reported an LD50 for 'Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear' in male and female rats >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
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
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

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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2014-01-08 to 2014-01-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar: (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 g
- Fasting period before study:
- Housing: housed individually during the exposure period; in groups of 5 by sex for the rest of the study period; housed in polypropylene cages
- Diet: 2014C Teklad Global Rodents diet, ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: 10 % of the total body surface area
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hout exposure period the area was wiped with cotton wool moistened with arachis oil BP
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: yes; 2.48 mL/kg


Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were examined at 30 min, 1, 2, and 4 hours post-application, and every day for the 14 day study period. Body weights were recorded prior to the treatment and at days 7 and 14.
- Necropsy of survivors performed: yes; at the end of the study the animals were killed by cervical dislocation; external examination and opening of the abdominal and thoracic cavities were performed at necropsy
- Other examinations performed: behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects were noted during the 14 day study period. The test sites were examined for evidence of primary irritation and scored.
Statistics:
No statistics were used in the study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occured.
Clinical signs:
No signs of systemic toxicity were observed.
Body weight:
All females showed no body loss or gain in body weight during the first week and expected gain in body weight in the second week. The males showed expected gain in body weight during the 14 day study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Slight desquamation was observed in 3 females on days 4, 5 and 6 of the 14-day study period.
Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

An acute dermal toxicity study for 'Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear' was performed to assess the acute dermal toxicity in rat.

A single dose of 2000 mg/kg bw of undiluted test material was applied onto the skin of 5 male and 5 female rats. The test item was held in contact with the skin under semi-occluded dressing for 24 hours. Observations for clinical signs of toxicity were performed at 30 min, 1, 2, and 4 hours post-application and every day for the 14 day study period. Body weights were recorded prior to the treatment and at days 7 and 14. At the end of the study the tested animals were killed by cervical dislocation. External examination and opening of the abdominal and thoracic cavities were performed at necropsy. Behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects were noted during the 14 day study period. The test sites were examined for evidence of primary irritation and scored.

No mortalities occured at during the 14 -day study period. There were no signs of systemic toxicity. All females showed no body loss or gain in body weight during the first week and expected gain in body weight in the second week. The males showed expected gain in body weight during the 14 day study period. No abnormalities were noted at necropsy.

The LD50 value for 'Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear' was concluded to be > 2000 mg/kg bw. The study was conducted according to OECD TG 402, and in compliance with GLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

On the basis of the available oral, inhalation and dermal data, the substance 'Paraffin Waxes (Fischer-Tropsch), full range, C15-50 - branched and linear' does not require classification for lethal effects following a single exposure according to Regulation 1272/2008/EC.

However, as a low viscosity hydrocarbon, there is a potential aspiration hazard following oral exposure to 'Paraffin Waxes (Fischer-Tropsch), full range, C15-50 - branched and linear'. It is therefore appropriate to classify product grades with kinematic viscosity ≤ 20.5 cSt at 40°C as Aspiration Toxicity Category 1 (H304) according to Regulation (EC) No 1272/2008.