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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guidelineopen allclose all
according to
OECD Guideline 403 (Acute Inhalation Toxicity)
according to
EPA OTS 798.1150 (Acute inhalation toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material


Test animals

Fischer 344
Details on test animals and environmental conditions:

- Source: Charles River WIGA GmbH, Sandhoferweg 7, D-97633 Sulzfeld, Germany

- Age at study initiation: 6-8 weeks

- Weight at study initiation: 126-150g males, 106-122g females

- Fasting period before study:

- Housing: Individual housing in Makrolon type 3 cages with standard softwood bedding.

- Diet: pelleted standard Kliba 343 rat maintenance diet, ad libitum.

- Water: community tap water (Geneva), ad libitum

- Acclimation period: 7 days


- Temperature (°C): 22 +/-3C

- Humidity (%): 30-70

- Air changes (per hr): 10-15

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
other: unchanged (no vehicle)
Details on inhalation exposure:

- Exposure apparatus: Inhalation exposure was performed according to the method of Sachsse et al. (1973, 1976). The test article stream reached the animal's nose through ports situated at different levels around the axis of the chamber. Each level has 8 ports and can be rotated, allowing close observation of all the animals without interruption of exposure. The flow-past, nose-only design of this exposure system is based upon the fluid dynamic modelling of the aerosol flow. It ensures a uniform test article distribution, provides a constant stream of "fresh" test article to each animal and precludes rebreathing the exhaled air.

- Exposure chamber volume: The internal active volume of the chamber for exposure up to 24 animals was approximately 0.7 litres.

- Method of holding animals in test chamber: The animals were confined separately in Makrolon tubes that are positioned radially around the exposure chamber.

- Source and rate of air: Airflow rate was 1.25-1.52 l air/minute per animals

- System of generating particulates/aerosols: The system consisted of a reservoir with test article for constant pressure feeding of nebulizer, a nebulizer, a glass chamber dilution system, a constant pressure airflow to nebulizer, flowmeter controlled airflow for test article dilution and an outlet to the nose-only exposure system.

- Temperature, humidity, pressure in air chamber: Samples for the measurements of the test article concentration (analytical, gravimetric), oxygen concentration, relative humidity and temperature were collected from a port of the exposure chamber, directly from the feed tube delivering 'fresh' test article to the animal's nose. Therefore, all the measurements were isoaxial and represented exactly what was delivered to the animals.


- Brief description of analytical method used: The relative test article concentration was measured during each exposure using a RAM-1 light scattering type aerosol device from GCA Corp., Bedford Massachusetts, U.S.A. The analytical determinations of the test article were performed using test atmosphere samples collected in wash bottles connected to the exhaust of the Gelman filter holder (used for gravimetric determinations.) The volatile phase of the test atmosphere was passed into three wash-bottles placed in series containing each 80 ml of n-fexame cooled at -70C. The content of each wash bottle was transferred into 100 ml volumetric flasks made up to 100ml with the rinsing. Aliquots of each wash bottle were put into appropriate sealed vials and sent for analysis at ambient temperature.

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)

- Particle size distribution: The distribution of the particle size in the aerosol was not measured due to the relatively low vapour pressure of the test article. Preliminary trials performed with an impactor produced unreliable results, due to partial evaporation of the test article during the course of the technical procedure.

Analytical verification of test atmosphere concentrations:
Duration of exposure:
4 h
8.10, 7.42, 10.91, and 15.87 (nominal). 4.62 mg/l, 6.73 mg/l, 9.82 mg/l, 15.37 mg/l (actual).
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical signs and mortality were noted during and following the exposures over a 15-day observation period. Body weights were recorded once during the acclimation period, on test day 1 prior to exposure, and on test days 2, 3, 4, 5,
6, 9, 12 and 15. Food consumption was measured once during the acclimation period (over 5 days), and during 8 intervals following the exposure (from days 1-2, 2-3, 3-4, 4-5, 5-6, 6-9, 9-12 and 12-15).

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: All animals were necropsied, and all macroscopic abnormalities recorded. The lungs, trachea, larynx, nasopharyngeal tissues, liver, spleen, thymus, lymph nodes (mandibular, mesenteric, mediastinal), salivary glands, as well as other organs with macroscopic findings were collected from all animals and fixed in a buffered solution. The lungs were instilled with fixative under a hydrostatic pressure of 30 cm. The lungs, liver, spleen and thymus of all surviving animals were weighed before fixation.
The LOGIT-Model (LOGIT: A program for dose response analysis, Koshiver J. and Moore D., Computer Programs in Biomedicine, 10, 1979, 61-75) was used to calculate the LC50.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
8.67 mg/L air
Based on:
test mat.
95% CL:
>= 7.3 - < 10.32
Exp. duration:
4 h
See Table 1.
Clinical signs:
Body weight:
In group 1, the mean body weight in both sexes was considered to be normal for animals of this strain and age, and to be unaffected by treatment. In group 2, the rats of both sexes showed practically no growth during the first observation week. Growth resumed during the second week, and the mean weight was considered as normal in both sexes at the time of the terminal sacrifice. In group 3, both surviving male and female rats showed a
moderate-to-marked weight loss during the first 2 or 3 days following exposure, then growth resumed. The male had not achieved a normal weight at the end of the 14-day observation period, whereas the weight of the female was considered as normal. Due to the death of all animals, no assessment was made in group 4.
Gross pathology:
No remarkable differences were observed in absolute/relative organ weights among all surviving animals. No significant findings were noted in the lungs of animals surviving the treatment period. In group 3, the lungs from the animals that died were reddish or dark red and incompletely collapsed. In group 4, the lungs from the animals that died were dark red and incompletely collapsed in one male and in 2 females. These findings were
considered to be treatment-related. The eyes of 4 males and 4 females from the high dose exposure group had a grey-white colouration, focal and general; this finding was considered to be treatment-related.
Other findings:
Food Consumption: In group 1, the mean food consumption in both sexes was considered to be normal for animals of this strain and age, and to be unaffected by treatment. In group 2, food consumption was slightly reduced in males during the first day following exposure and moderately reduced in females during the first two days following exposure. Then food consumption returned to normal values in both sexes. In group 3, no data are available for both surviving male and female rats for the first 2 days following exposure (due to technical error). In the male, food intake was low until
day 5 and then returned to normal. In the female, it was considered as normal from the first days when record was available (day 3). Due to the death of all animals, no assessment could be made in group 4.

Any other information on results incl. tables

Table 1: Concentrations, exposure conditions and mortality per animals treated


Conc. (mg/L)

Mortality (# dead/total)





















Exposure Concentrations: Results of the nominal, gravimetric and analytical determinations 

of decamethylcyclopentasiloxane measured for the four exposure groups are summarized below.  

As gravimetric concentrations correspond to the liquid phase, and analytical concentrations 

to the vapor phase of the test article, the results were added.  Except for the lowest 

exposure concentration, good agreement was found between the sum of gravimetric and 

analytical values and nominal concentrations.  

Test Atmosphere Concentrations (mg/L air)
Group   Nom.(1)  Grav.(2)   Analyt.(3)   Total(4)
1       8.10     2.53       2.09         4.62
2       7.42     4.49*      2.24*        6.73*
3       10.91    7.54*      2.28*        9.82
4       15.87    13.58*     1.79*        15.37*

*Mean of two values.
Nom= nominal; Grav = gravimetric; Analyt = analytical
(1): Concentrations based upon the amount of test article used during the exposure period.
(2): Corresponds to the liquid phase of the test atmosphere collected on the Gelman filters.
(3): Corresponds to the vapor phase of the test atmosphere collected in n-hexane.
(4): Total of 2 and 3.  The values were used to calculate the LC50.

Exposure Conditions: The temperature, relative humidity and oxygen concentration ranges 

in the test atmosphere measured during the exposure periods are given below:

Groups  Temp.      RH        O2
        (degC)     (% rh)   (vol %)
1     19.8 - 20.7  3.8-5.2  20.8-20.9
2     20.4 - 21.1  5.3-7.6  20.8-21.0
3.    20.8 - 21.6  4.9-5.3  20.7-20.8
4     18.5 - 19.1  5.9-6.9  20.8-20.9         
RH= relative humidity; O2 = O2 concentration

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
An acute inhalation LC50 value of 8.67 mg/L was determined for male and female rats in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.