Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-10-07 to 2011-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Version / remarks:
1998
GLP compliance:
no
Remarks:
(Lab. closed before GLP-Konformation)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
DYNAPOL Katalysator 1203
> 99% Neodecanoic acid, oxiranylmethyl ester, polymer with 4-methylbenzenesulfonic acid
ca. 1 % other ingrediants: p-, m-, o-, Xylene and Ethylbenzene

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS: 
- Strain: Rattus norvegicus) / CD / Crl: CD(SD)
- Source: Charles River Laboratories, 97633 Sulzfeld, Germany
- Age: 8 to 9 weeks at time of administration
- Weight at study initiation: males: 317.4 g, females: 244.9 g
- Number of animals: 5 males and 5 females
- Housing: single caging
- Diet: ad libitum, ssniff R/M-H V 1534
- Water: ad libitum, tab water
- Acclimatisation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): mean 20.8 °C
- Humidity (%): mean 41.7 %
- Photoperiod (hrs dark / hrs light): 12 hours darkness, 12 hours artifical light
- Air exchange: about 12/h

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
- Type of exposure: nose-only, using a Head Nose Only Exposure Unit from TSE-Systems GmbH, Bad Homburg, Germany
- Method of holding animals in test chamber (volume 24 l): In ten openings of the chamber, the inhalation tubes with the animals were situated.
- Type or preparation of particles: For aerosol generation am aerosol nozzle was used. Test substance – ethanol mixtures (1+9) were dosed with a
syringe pump and sprayed by an nozzle. The desired aerosol concentrations were obtained by controlling the feed rate of the syringe pump. The
nozzle was placed into a separator which was fixed on the upper centre of the inhalation chamber. Larger droplets sediment within the separator
and smaller ones followed the air stream to the outer chamber and reached the animals
- Method of particle size distribution: The size of the aerosol particles was analysed twice during the exposure with a cascade impactor
(Berner-Impaktor Type LPI4/0,06/2 from Hauke KG, Gmunden, Austria). It contains nine steps with cut-off- diameters from 0.06 µm to 16 µm.
The cut-off diameters were obtained from the manufacturer. 5.65 litres/minute of the test substance - air mixture were passed through the
impactor and the amount which sediment in the individual steps was determined gravimetrically. The site of collection was the same as for the
analysis.
The calculated mass median aerodynamic diameter (MMAD) of the test substance aerosol was 2.0 and 1.96 µm.
- Temperature, humidity: T: 19.3 to 19.7°C, H: 47.5 % to 47.9 %
TEST ATMOSPHERE
- Concentrations: 1.9 mg/l, the maximal obtainable aerosol concentrations were only about 1.9 mg/L and therefore below the limit concentration of 5 mg/L.
- Flow (L/min): 5.65 litres/minute of the test substance - air mixture were passed through the impactor
- Air flow: 17.2 L/min

Analytical verification of test atmosphere concentrations:
yes
Remarks:
The concentration of the aerosol was detected 7 times during the exposure period
Duration of exposure:
4 h
Remarks on duration:
4 hours
Concentrations:
The mean actual aerosol concentration was 1.9 mg/L.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
EXAMINATIONS: 
- Post dose observation period: 14 days
- body weights: before,  1, 7 and 14 days after treatment   
- behavior/clinical signs/mortality: 1, 2, 3, 4, 5, and 6 hours after start of exposure and then at least once a day for a total of 14 days 
- Necropsy: Surviving animals were killed by CO2-asphyxia (80 % CO2 and 20 % air) and subjected to a necropsy including a gross pathological
examination.
Statistics:
not necessary

Results and discussion

Preliminary study:
Before starting the test, the following experiments were made to obtain more information about the test substance:
- It was tried to produce an aerosol with an actual concentration of about 5 mg respirable test substance per litre.
- Two animals were exposed to an aerosol of the test substance to get first information about its possible toxicity.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.9 mg/L air
Exp. duration:
4 h
Mortality:
All animals survived till the end of the study.
Clinical signs:
No abnormal observations were seen in any animal during the 14 days observation period.
Body weight:
The body weight and weight gain was inconspicuous in all animals. The body weight loss the first days after the expose which was seen in most
animals is caused by the restraining in the inhalation tube and not necessarily test substance related. No adverse effect of the test substance can
be derived from the body weight data.
Gross pathology:
Nothing abnormal was seen in any of the animals.
Other findings:
no other findings

Any other information on results incl. tables

no further remarks


Applicant's summary and conclusion

Conclusions:
The LC50, per inhalation, four hours exposure, of test item for male and female rats is therefore greater than 1.9 mg/L air which is the highest technically feasible aerosol concentration.
Executive summary:

It was the aim of this study to reveal acute toxic effects of test item after a single administration per inhalation as a liquid aerosol.

Test item was administered as aerosol with a mass median aerodynamic diameter of 2.0µm per inhalation to Sprague Dawley rats. The test substance was applied for 4 hours in a nose-only inhalation device. The actual concentration of the aerosol was1.9mg per litre air which is under the limit concentration for this kind of tests. Five male and fivefemale animals were exposed. The inhalation exposure of rats to test item at the maximal technically feasible concentration of 1.9 mg/L did not produce signs of toxicity. All animals survived and no adverse effects were observed during the 14-day observation period.

The LC50, per inhalation, four hours exposure, of test item for male and female rats is therefore greater than 1.9 mg/L air which is the highest technically feasible aerosol concentration.