Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Only one dose, 5 mg/m3, top dose for vapours according to guideline version of 1981 but insufficient by today's gudieline version. Study does not meet the current classification cut-offs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
modified: whole-body, 5M/5F, one dose of 5 mg/l (vapour)
Deviations:
yes
Remarks:
but not considered to have impacted the study outcome. (page containing Table with deviations missing)
GLP compliance:
yes
Remarks:
US-EPA TSCA GLP 40 CRF part 792
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
5 male, 5 female rats, strain Sprague-Dawley, Crl:CD(SD)IGS;
At strat of study: age 9 weeks;
body weights females 201.8 - 227.7 grams;
body weights males 298.1-334.5 grams;
one group only;
identification by eartags and indivudual cage labels;
individually housed in wire-meshe cages elevated above absorbent material, regularly cleaned in accordance with good animal husbandry;
environmentally controlleed animal rooms;
artificial lighting, light/dark 12/12;
temperature 22+-3 degr.C , 30-70% relative humidity, 10-15 air changes /hr;
certified rodent deit ad lib except during exposure. reverse-osmosis purified tap water at lib.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Remarks:
source: Nash air compressor AL-574; serial filters Matheson 460/461 and Balston 100-118-DX and 100-8-BX.Dilutuion air stream: HEPA-filtered, activated carbon filtered, warmed and humidified room air.
Details on inhalation exposure:
whole- body exposure.
limit test.
target concentration 450 ppm = 5 mg/l.
measured concentrations 445 ppm= 4.9 mg/l.
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rochester-type, Stainless steel and glass whole-body exposure chamber;
- Exposure chamber volume: 450 liters;
- Method of holding animals in test chamber: stainless steel mesh caging;
- Source and rate of air: Room air, mean chamber airflow rate 105 +- 0.8 L/min. (14 air changes /hr) dilution air stream;
- method of conditioning; HEPA-filtered, activated carbon filtered, warmed and humidified room air;
- Temperature: 24.1 +-1.2 degr C;
- humidity: 49.7 +- 3% RH;
- pressure in air chamber:
- oxygen content: 20.9 degr. C;
TEST ATMOSPHERE
- Brief description of analytical method used: Varian Gas chromatograph 3400 with GC/IFD; one sample /30 minutes. Calibrated using 5 levels of bag standards in the range of 250-650 ppm;
- Samples taken from breathing zone: No.

VEHICLE
- Composition of vehicle: compressed, filtered air:

Analytical verification of test atmosphere concentrations:
yes
Remarks:
See above for analytical method details. measured concentration showed good correlation with calculated nominal concentrations (4.3% difference)
Duration of exposure:
ca. 280 min
Remarks on duration:
20 minutes lead time to build up to min. 99% of target concentration; 20 minutes end lag time to reduce concentrations to max 1% of target concentrations.
Concentrations:
mean measured chamber concentration: 4.9 +- 0.2 mg/l (445 +- 16.6 ppm)
See table in "any other observations on results"
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:Mortality twice daily, once during weekends. Clinical signs: once daily
- Frequency of weighing: day1, prior to exposure; day 8; day 15 (prior to sacrifice)
- Necropsy of survivors performed: yes (complete gross pathology examination)
Statistics:
not applicable: no mortality

Results and discussion

Preliminary study:
not performed.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LC50
Effect level:
> 4.9 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Also incuding 20 min. lead time and 20 min. lag time
Sex:
male
Dose descriptor:
LC50
Effect level:
> 4.9 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Also incuding 20 min. lead time and 20 min. lag time
Mortality:
None
Clinical signs:
other: None
Body weight:
Body weight ranges and body weight gains were within acceptable ranges throughout duration of the study (barring one deviation) (Table individual body weight gains missing)
Gross pathology:
No gross pathology findings
Other findings:
none reported

Any other information on results incl. tables

Conditions during exposure.

Time point (30 min. intervals)

Measured conc. (ppm)

Measured conc. (mg/l)

Temperature

(°C)

Humidity (%RH)

Air flow (L/min)

1

N.A.

N.A.

21.6

53.1

106

2

414

4.5

22.7

53.2

106

3

425

4.7

23.3

51.5

105

4

444

4.9

23.9

47.4

105

5

446

4.9

24.7

44.8

105

6

446

4.9

25.0

48.4

105

7

460

5.0

25.0

53.7

105

8

444

4.9

24.8

48.8

105

9

456

5.0

24.9

48.2

105

10

467

5.1

24.8

48.0

103

Mean

445

4.9

24.1

49.7

105

SD

16.6

0.2

1.2

3.0

0.8

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substane is a mixture of the submission substance, 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-88-9) and 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5). These substances are structurally very closely related and, as shown in the hydrolysis test (see 5.1.2) will probably result in similar or identical hydrolysis product in contact with water. The results for the mixture are therefore considered to be applicable to both substances individually. No mortality was seen after a 4-hour exposure to a mean measured concentration of 4.9 mg/l or during a 14-day observation. The LC50 is considered to be greater than 4.9 mg/l.

The selected single dose is in the range of 2
Executive summary:

An acute inhalation study was performed with a mixture of 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane. Five male and five female animals were exposed in a whole-body exposure chamber for 4 hours and subsequently observed for 14 days. Only one dose was tested: nominal 5 mg/l, measured 4.9 mg/l. No mortalitiy or any clinical signs were observed. The LC50 of the mixture is > 4.9 mg/l.