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Toxicological information

Acute Toxicity: inhalation

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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:
comparable to guideline study with acceptable restrictions
Remarks:
Study according to modified OECD 403 protocol, no deviations with impact on study outcome. - Test substance identified as mixture of 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-99-0) , exact composition not given . However, the study owner has confirmed that the test substance was a mixture of 54% 2370-88-9 Tetramethylcyclotetrasiloxane, 45% 6166-86-5 Pentamethylcyclopentasiloxane and the impurity 0.9% Hexamethylcyclohexasiloxane - Name of testing facility and Study Director unknown - pages 19-22 missing (tables: individual animal observations; individual animal weight gains; summary of protocol deviations) - only one dose, 5 mg//m3, top dose for vapours according to guideline version of 1981 but insufficient by today's guideline version. Study does not meet the needs of current classification cutoffs.

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
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 start of study: age 9 weeks.
body weights females 201.8 - 227.7 grams
body weights males 298.1-334.5 grams
one group only
indentification 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 controlled animal rooms
artificial lighting, light/dark 12/12
temperature 22+-3 degr.C , 30-70% relative humidity, 10-15 air changes /hr
certified rodent diet 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 pppm
- 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. 240 min
Remarks on duration:
20 minutes lead time to build up to min. 99% of target concentration; 240 minutes at 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
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
> 4.9 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 4.9 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
None
Body weight:
Body weight ranges and body weight gains were within acceptable ranges thoughout 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)

Tempera-ture

(°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:
Category 3 based on GHS criteria
Conclusions:
The test substance is mixture of the submitted substance, 2,4,6,8,10-pentamethylcyclopentasiloxane (CAS 6166-86-5) and 2,4,6,8-tetramethylcyclotetrasiloxane (CAS 2370-99-0). 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 products in contact with water. The results are therefore considered to be applicable to both substances. No mortality was seem 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 . Based on the criteria in the CPL regulation (EC) No 1272/2008, the substance must be classified in the acute hazard category 3.
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. 5 male and 5 female animals were exposed in a whole-body exposure chamber for 4 hours and subseqently observed for 1 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.