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Toxicological information

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:
key study
Study period:
1995-03-10 to 1995-03-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it was conducted according to OECD 403 guidelines and was GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
This substance is very similar with regard to health endpoints to the substance being registered.
- Name of test material (as cited in study report): Alkane 4
- Substance type: Poly Alpha Olefin (1-dodecene trimer, hydrogenated)
- Physical state: Liquid
- Analytical purity: Not reported
- Lot/batch No.: C1527-04-4
- Stability under test conditions: Not reported
- Storage condition of test material: Room temperature
- Other: Clear colourless liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (U.K.) Ltd (Kent, U.K.)
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: Male: 265 to 342 grams; Female: 219 to 263 grams
- Fasting period before study: Only during exposure
- Housing: Groups of 5 in polypropylene grid-floor cages
- Diet (e.g. ad libitum): Rat and Mouse Expanded Pelleted Diet No. 1 (Special Diet Services Limited (Essex, U.K.) ad libitum except during exposure
- Water (e.g. ad libitum): Ad libitum except during exposure
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23°C
- Humidity (%): 46 to 52%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

IN-LIFE DATES: From: 1995-03-10 To: 1995-03-26

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass concentric jet nebuliser (Radleys, Essex, U.K.)
- Exposure chamber volume: 30 Litres
- Method of holding animals in test chamber: Tapered polycarbonate restraining tube fitted onto a single tier of the chamber and sealed with a rubber 'o' ring
- Source and rate of air: Compressed air supplied from a 'Gast' oil free compressor at the rate of 16 Litres/min
- Method of conditioning air: Air was passed through a water trap and respiratory quality filters to remove particulate material >0.005µm
- System of generating particulates/aerosols: Test material was aerosolized in a jet nebulizer connected to a glass syringe that was attached to a modified infusion pump.
- Method of particle size determination: Cascade Impactor
- Treatment of exhaust air: Metered exhaust system connected to a high efficiency filter prior to which exhaust air passed through a 'scrubber' trap
- Temperature, humidity, pressure in air chamber: Temperature and relative humidity measured by an electronic thermometer/humidity meter (kane-May Ltd. Hertfordshire, U.K.)


TEST ATMOSPHERE
- Brief description of analytical method used: The chamber concentration was estimated at regular intervals during the exposure period. The gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump for a suitable time period. Each filter was weighed before and after sampling in order to calculate the weight o f collected test material. The difference in the two weights divided by the volume of atmosphere sampled was the chamber concentration.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 90.1% inspirable fraction <4 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD - 1.2µm; GSD - 0.40µm

Analytical verification of test atmosphere concentrations:
yes
Remarks:
5.06 mg/L
Duration of exposure:
ca. 4 h
Concentrations:
5 mg/L
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical Toxicity - hourly during exposure, immediately subsequent to exposure, 1 hour post exposure and then once daily for the 14 day observation period; Body weight - day 0, 7, and 14
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight
Statistics:
Mean values and standard deviation were calculated for chamber atmosphere concentration and particle size distribution.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.06 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: Based on lack of mortality or signs of adverse clinical toxicity
Mortality:
There was no mortality observed in either male or female rats exposed nose-only to Alkane 4 for 4 hours.
Clinical signs:
other: Clinical signs occurred after removal from the exposure chamber and included wet fur, hunched posture and pilo-erection, increased respiration rate, ptosis, and isolated incidents of decreased respiration rate and red/brown stain on the head. One hour af
Body weight:
There were no treatment-related changes observed in body weight.
Gross pathology:
At terminal sacrifice, there were no gross abnormalities observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute LC50 for Alkane 4 is >5.06 mg/L based on the lack of adverse clinical toxicity and mortality observed in male and female rats.
Executive summary:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for the poly alpha olefin 1-decene trimer and tetramer hydrogenated (CAS number 68649-12-7) using alkane 4 (1-dodecene, trimer, hydrogenated) as an analog. Both of these compounds are poly alpha olefins, i.e., highly branched isoparaffinic chemicals produced by oligomerization of 1-octene, 1-decene, and/or 1-dodecene. They have similarities in chemical structure and physiochemical properties. The literature also indicates that alkanes with 30 or more carbon atoms are unlikely absorbed when administered orally. In turn, studies indicate that they have similar health effect endpoints. Both of these poly alpha olefins have low order acute toxicity and repeated dose toxicity. Additionally gene mutations assays in bacterial cells, as well as in vitro chromosomal aberrations in mammalian cells assays demonstrate no evidence of genotoxicity regardless of metabolic activation. In vivo chromosomal aberrations assays in rats and mice also show no mutagenic potential regardless of metabolic activation. There do not appear to be any toxicological differences between 1-decene trimer and tetramer hydrogenated and alkane 4. Therefore, read across between 1-decene trimer and tetramer hydrogenated and alkane 4 can be justified.

\In an acute inhalation toxicity study, young adult Sprague-Dawley rats (5/sex) were exposed by inhalation route to Alkane 4 in (in air) for 4 hours to (nose only) at concentrations of 5.06 mg/L. Animals then were observed for 14 days.

 

Clinical signs occurred after removal from the exposure chamber and included wet fur, hunched posture and pilo-erection, increased respiration rate, ptosis, and isolated incidents of decreased respiration rate and red/brown stain on the head. One hour after exposure, the only observable clinical signs included hunched posture, pilo-erection, and increased respiration rate. By day 2 post exposure, all animals had recovered and appeared to be normal. There were no treatment-related changes observed in body weight. At terminal sacrifice, there were no gross abnormalities observed. Based on these results, the LC50 is greater than 5.06 mg/L.

 

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it was conducted according to OECD 403 guidelines and was GLP compliant.