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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:
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:
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:
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals 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:
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.