Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 Sep - 02 Oct 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Behörde Soziales, Familie, Gesundheit und Verbraucherschutz, Hamburg, Germany
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane
EC Number:
306-085-3
EC Name:
Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane
Cas Number:
95912-89-3
Molecular formula:
not applicable, UVCB
IUPAC Name:
Fatty acids, C8-10 (even numbered), mixed esters with adipic acid and trimethylolpropane
Details on test material:
- Name of test material (as cited in study report): Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane
- Physical state: light yellowish, clear liquid
- Analytical purity: 100%
- Lot/batch No.: OE10428
- Storage condition of test material: at room temperature, in a tightly closed container; kept away from heat, sparks, flames and direct sunlight

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Age at study initiation: 8 weeks (males), 9 weeks (females)
- Weight at study initiation: 243-260 g (males), 221-231 g (females)
- Fasting period before study: animals were fasted for approx. 16 h before administration.
- Housing: animals were kept by sex in groups of 2-3 animals in MAKROLON cages (type III plus), bedded with granulated textured wood (Granulat A2, J. Brandenburg, Goldenstedt, Germany).
- Diet: commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 Sep 2012 To: 02 Oct 2012

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 apparatus: dynamic inhalation chamber (RHEMA-LABORTECHNIK, Hofheim, Germany) with cylindrical exposure chamber
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: in pyrex tubes at the edge of the chamber in a radial position
- Source and rate of air: compressed air (5.0 bar) from a compressor at a flow rate of 900 L/h (entrance) and 800 L/h (exit)
- System of generating particulates/aerosols: spray-jet (Type 970, Düsen-Schlick GmbH, Untersiemau, Germany)
- Method of particle size determination: cascade impactor according to May
- Treatment of exhaust air: exhaust air was sucked through gas wash-bottles.
- Temperature, humidity, pressure in air chamber: 21.2° C, 61.5%

TEST ATMOSPHERE
- Brief description of analytical method used: the actual aerosol concentration in the inhalation chamber was measured 4 times gravimetrically with an air sample filter (Minisart SM 17598; 0.45 µm) and pump (Vacuubrand, MZ 2C ) controlled by a rotameter. Aerosol samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses in the inhalation chamber and air was sucked through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling on an analytical balance.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle: 21% v/v oxygen content in the air

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see Table 1 under “Any other information on materials and methods incl. tables”
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 4.481 µm / 3.19
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
5.05 mg/mL (analytical concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: examination of clinical signs and mortality were performed at least once daily. Body weights were determined before exposure on Day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Mean values and standard deviations of temperature, humidity and analytical concentration were calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.05 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was observed during the whole study period.
Clinical signs:
other: Slight ataxia, slight tremor and slight dyspnoea occurred immediately until 30 min or 3 h after end of exposure in all male and female animals.
Body weight:
No treatment-related body weight effects were seen and all animals showed the expected gain in body weight.
Gross pathology:
No pathological findings were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified