Decamethyltetrasiloxane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 October 2005 to 23 January 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study did not meet current guideline requirements for acute inhalation toxicity. It does, however, add weight of evidence for this endpoint. The study itself could be considered reliability 1, but when used as a substitute for an acute toxicity study it has been assigned reliability 2.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 440 (Uterotrophic Bioassay in Rodents)

Deviations:

not applicable

Principles of method if other than guideline:

Uterotrophic assay in which ovariectomized adult Sprague-Dawley rats were exposed to decamethyltetrasiloxane (L4) at 400 ppm (study group 10) or to air (study group 1) for 6 hours following subcutaneous injection with corn oil.

GLP compliance:

yes

Test type:

other: short-term inhalation study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Decamethyltetrasiloxane

EC Number:

205-491-7

EC Name:

Decamethyltetrasiloxane

Cas Number:

141-62-8

Molecular formula:

C10H30O3Si4

IUPAC Name:

2,2,4,4,6,6,8,8-octamethyl-3,5,7-trioxa-2,4,6,8-tetrasilanonane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: ~62 days at start of exposure
- Weight at study initiation: 260.5 to 292.9 g (individual animal body weights in groups 1 and 10, immediately prior to inhalation exposure)
- Fasting period before study: fasting during inhalation exposure
- Housing: individually in suspended wire-mesh cages elevated above fecal pans
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum purified municipal water
- Acclimation period: 4 days
- Other: animals were ovariectomized 20 days prior to inhalation exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.81 to 22.48
- Humidity (%): 39 to 57
- Air changes (per hr): ~ 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data available

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel and glass Rochester-style inhalation chambers and stainless steel exposure caging
- Exposure chamber volume: 2000 litres
- Method of holding animals in test chamber: stainless steel exposure caging compartments
- Source and rate of air: 10-15 air changes of chamber volume per hour
- Method of conditioning air: no data available
- System of generating particulates/aerosols: heated stainless steel J-tube containing a column of stainless steel beads. Test material was metered from a reservoir into the J-tube using a Fluid Metering Incorporated (FMI(R)) pump.
- Treatment of exhaust air: no data available
- Temperature, humidity, pressure in air chamber: 22.9-25.5 °C, 31 to 56.1%

TEST ATMOSPHERE
- Brief description of analytical method used: air sampled, then tested with gas chromatography with flame ionisation detection, with each chamber evaluated at least once per hour during the exposure period
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

400 ppm (nominal)

No. of animals per sex per dose:

8 females/group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: ~18 hours
- Frequency of observations and weighing: twice daily mortality, morbidity and moribundity checks. Body weight taken prior to subcutaneous dosing and again after approximately 24 hours.
- Necropsy of survivors performed: no (not after a single 6-hour exposure. But after the 3rd exposure, the uterus was weighed and examined histologically)
- Other examinations performed: clinical signs, body weight

Statistics:

All data analysis was carried out using SAS version 8.2. Statistically significant probabilities were reported for p-values of <0.05, <0.02 and <0.01. ANOVA was used to compare dose group to controls for all endpoints assuming a normal distribution. Pair-wise comparisons to controls were performed using Dunnett's test.

Results and discussion

Preliminary study:

no data available

Effect levels

Sex:

female

Dose descriptor:

LC50

Effect level:

> 400 ppm

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: No clinical signs of toxicity or changes in body weight were seen by 18 hours after the end of exposure; 400 ppm = 5080 mg/m3

Mortality:

All animals survived.

Clinical signs:

other: No substance-related clinical signs were noted. A pea-sized blood area was seen on the left side of the neck of one control animal.

Body weight:

No statistically significant difference in body weight was seen between treated animals (mean 280.23 g, standard deviation 8.71) and controls (mean 279.90, standard deviation 9.73).

Gross pathology:

No changes in the weight or histology of the uterus were seen at necropsy after the 3rd 6-hour inhalation exposure to L4 compared with inhalation of air.

Other findings:

No data available.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

In a non-guideline study, designed to investigate the anti-estrogenic activity of decamethyltetrasiloxane (L4) and performed to GLP, no overt toxicity was seen in ovariectomized female rats exposed at 400 ppm for 6 hours.

Executive summary:

In a non-guideline study, designed to investigate anti-estrogenic activity and performed according to GLP, rats were exposed to decamethyltetrasiloxane (L4) by inhalation.

 

Eight female ovariectomized rats per group were given subcutaneous injections of corn oil (2 ml/kg bw) followed by whole-body exposure to decamethyltetrasiloxane (L4) at 400 ppm or air for 6 hours. Animals were observed twice daily for clinical signs and mortality, and body weights were recorded prior to treatment and again after approximately 24 hours.

 

No mortality or adverse clinical signs of toxicity, or significant effects on body weight were seen in treated rats within approximately 18 hours following exposure.