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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated 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:
other: see 'Remark'
Remarks:
The study does not comply fully with the specific testing guideline. However, the study is well documented and the method used is scientically acceptable. The information in the publication is used to support the waiver. 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:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
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 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 levelsopen allclose all
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
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
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
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
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.