[No public or meaningful name is available]

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The study does not comply fully with the specific testing guideline. However, the study is well documented and the method used is scientifically acceptable. The information in the publication is used to support the waiver.

Justification for type of information:

Read-across justification: Based on the chemical composition, the renewable hydrocarbons produced from raw materials such as fatty acid rich oil like Crude Tall Oil (CTO) or triglyserides, using a hydrotreatment process have similar hydrocarbon fractions and they contain the same critical constituents than fossil diesel fuels. According to the identified hydrocarbon blocks, the typical carbon number ranges and the physicochemical properties, the renewable hydrocarbons with diesel type fractions can be considered as having structural similarities and similar behaviour in contact with water and in the physiological processes than the analogue source substances (fossil diesel fuels). Their irritation properties, skin sensitisation property as well as acute and long-term adverse effects to human health is similar. Therefore, and in order to avoid the unnecessary animal testing, the read-across data from the analogue fossil diesel fuels is used to evaluate skin and eye irritation, the genetic toxicity, carcinogenicity, developmental toxicity and short term and/or long-term toxicological effects of the target substance.

Data source

Reference

Reference Type:

publication

Title:

Toxicity of n-C9 to n-C13 Alkanes in the Rat on Short Term Inhalation

Author:

Nilsen, O.G., Haugen, O.A., Zahlsen, K., Halgunset, J., Helseth, A., Aarset, H. and Eide , I.

Year:

1988

Bibliographic source:

Paharmacology and Toxicology, 62, 259-266

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Male Sprague Dawley rats were exposed to inhaltion of n-C9 to n-C13 alkanes close to air saturation at 20 deg. C (4438, 1369, 442, 142 and 41 ppm, respectively) for 8 hours and observed for the following 14 days. In addition, exposure to higher and lower concentrations of n-C9 alkane was performed.

GLP compliance:

not specified

Test type:

other: Modification of the standard method

Test material

Test material information

Constituent 1

Reference substance name:

Nonane

EC Number:

203-913-4

EC Name:

Nonane

Cas Number:

111-84-2

Molecular formula:

C9H20

IUPAC Name:

nonane

Constituent 2

Reference substance name:

Decane

EC Number:

204-686-4

EC Name:

Decane

Cas Number:

124-18-5

Molecular formula:

C10H22

IUPAC Name:

decane

Constituent 3

Reference substance name:

Undecane

EC Number:

214-300-6

EC Name:

Undecane

Cas Number:

1120-21-4

Molecular formula:

C11H24

IUPAC Name:

undecane

Constituent 4

Reference substance name:

Dodecane

EC Number:

203-967-9

EC Name:

Dodecane

Cas Number:

112-40-3

Molecular formula:

C12H26

IUPAC Name:

dodecane

Constituent 5

Reference substance name:

Tridecane

EC Number:

211-093-4

EC Name:

Tridecane

Cas Number:

629-50-5

Molecular formula:

C13H28

IUPAC Name:

tridecane

Details on test material:

n-C9 to n-C13 alkanes: n-nonane, n-decane, n-undecane, n-dodecane, n-tridecane. Measured purity (GC analysis) of the test samples varied between 99.65 - 99.89 %.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mollegaard A/S, Ll. Skensved, Denmark
- Weight at study initiation: 180-220 g
- Acclimation period: 4-6 d
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: conical 0.7 m3 steel chambers with glass front door and walls; flow rate 30-40 l/min.
- Vapour generation: test substance warmed (approx. 22 degrees C) under negative pressure and mixed with clean air to achieve required concentration
- Method of particle size determination:The presence of alkane aerosol in the inhalation chamber during exposure was investigated by Royco mod. 255 particlem onitorwith an aerosol particle counter sensor mod 241
- Temperature, humidity, pressure in air chamber: slightly higher than in the vapour generation, negative pressure 2-5 mm H20.

TEST ATMOSPHERE
- Brief description of analytical method used:Concentration of alkanes in the chambers was monitored automatically every 15 min by on-line gas chromatography (Shimadzu GC-9A).Chromatography was performed at 200 deg C on a 2 m x 1/8" stainless steel column packed with GP 10% SP-2100 on Supelcoport 100/120 mesh with helium as the carrier gas. The alkanes were detected by a FID detector. Injector and detector temperatures were 250 deg C.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

8 h

Concentrations:

n-C9: 5280*, 4438, 3560 and 2414 ppm
n-C10: 1369* ppm
n-C11: 442* ppm
n-C12: 142* ppm
n-C13: 41* ppm
Values marked * were the maximum achievable vapour concentration in air

No. of animals per sex per dose:

10 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: Animals were exposed to at least the saturated vapour concentration (20 degrees C) for each test substance for 8 hr.
- Frequency of observations and weighing: During inhalation all animals were observd at 15 and 30 min intervals. For the first 8 hours after exposure all animals were observed hourly, then at 2 hour intervals during daytime for 14 days.
- Necropsy of survivors performed: yes, full gross necropsy on day 14
- Other examinations performed: clinical signs, histopathology, body weight, tissue weights of brain, lungs, heart, liver and kidney, the LC50 for n-nonane was calculated by probit analysis.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

4 467 ppm

Based on:

test mat.

Remarks:

n-nonane

Exp. duration:

8 h

Remarks on result:

other: 23.4 mg/l

Effect levels 2

Sex:

male

Dose descriptor:

LC0

Effect level:

1 390 ppm

Based on:

test mat.

Remarks:

n-decane

Exp. duration:

8 h

Remarks on result:

other: 8.7 mg/l

Effect levels 3

Sex:

male

Dose descriptor:

LC0

Effect level:

442 ppm

Based on:

test mat.

Remarks:

n-undecane

Exp. duration:

8 h

Remarks on result:

other: 2.7 mg/l

Effect levels 4

Sex:

male

Dose descriptor:

LC0

Effect level:

142 ppm

Based on:

test mat.

Remarks:

n-dodecane

Exp. duration:

8 h

Remarks on result:

other: 0.99 mg/l

Effect levels 5

Sex:

male

Dose descriptor:

LC0

Effect level:

41 ppm

Based on:

test mat.

Remarks:

n-tridecane

Exp. duration:

8 h

Remarks on result:

other: 0.31 mg/l

Mortality:

n-nonane: 0/10, 1/10, 4/10, 9/10 at 2414, 3560, 4438 and 5280 ppm, respectively
n-decane, n-undecane, n-dodecane, n-tridecane: no mortality at maximum saturated vapour concentration

Clinical signs:

other: Tremor, spasms and limb paralysis were observed in rats treated with n-nonane. Most severe symptoms were observed in a high dose group. These symptoms were observed at 2 hours after the start of the exposure in the highest dose group. The length of time b

Body weight:

Not reported in the publication

Gross pathology:

No gross pathological changes were observed in the brain, lungs, heart, liver and kidneys following exposure to the n-C10 to n-C13 alkanes. In animals exposed to 4438 ppm of n-nonane the autopsy findings suggest that death was due to cardiopulmonary insufficiency. This may have been induced by the direct toxic effect of heart or lungs or by indirect effects by the central nervous system. In cerabellar cortex severe damage and extensive loss of purkinje neurons were demontrated.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50(rat, male) for n-nonane was 4467 ppm (23.4 mg/l) following 8-hr exposure.

Executive summary:

The acute inhalation toxicity of a series on C9-C13 n-alkanes were investigated in male SD rats following a single 8 -hr exposure to vapour. A calculated LC50 of 4467 ppm (23.4 mg/l) was determined for n-nonane; the 4 -hr LC50 value is likely to exceed this value. No mortality was recorded for the other test substances after exposure to the maximum achievable vapour concentration in air. Maximum saturated vapour concentration decreased in a predictable manner with increasing C-number.

The study was conducted for the read-across substance. This study is considered reliable since the publication contains sufficiently data for assessment.