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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:
comparable to guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
equivalent or similar to
other: OECD Guideline 412 (Repeated Dose Inhalation Toxicity: 28/14-Day)
(exposure only for 14-days; no particle sizing data; no clinical pathology)
GLP compliance:
Test type:
other: subacute
Limit test:

Test material


Test animals

Details on test animals and environmental conditions:
- Source: Charles River Breeding Laboratories, Portage, Michigan
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 100-160g
- Housing: individually housed in suspended stainless steel wire mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

- Temperature (°C): 25-29
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
clean air
Details on inhalation exposure:
Exposures were conducted in 450 litre stainless steel whole body exposure chambers. The chambers were operated under dynamic conditions where the chamber air wsa room air, which had been filtered (hepa and charcoal filters). The airflows through the chambers were kept at ca. 12-15 air changes per hour. Chamber temperature, humidity and airflow were monitored continuously and were recorded every five minutes by the Camile Data Acquisition System during the daily exposure period. The test material was introduced into the chambers through special mdesigned glass J - tubes. The test material was metered into tje J-tubes with FMI lab pumps. Instrument air which was filtered flowed through the J-tubes at a controlled rate. The air/vapour mixture passed into the inlet port at the top of the chambers. During the exposure periods attempts were made to keep the actual concentrations of the test material in the chambers as constant as possible. The duration of each exposure period was six hours after equilibration of the chamber concentration. The equilibration time, which is a function of chamber airflow, was ca. 20 minutes.
Analytical verification of test atmosphere concentrations:
Duration of exposure:
6 h
Remarks on duration:
5 days/week, 10 days over two weeks
5, 50 or 246 ppmn (analytical)
5, 50 or 250 ppm (nominal)
No. of animals per sex per dose:
Control animals:
Details on study design:
All animals were observed daily during the post-exposure period for treatment-related signs of toxicity, in particular any evidence of respiratory, dermal, behavioural, nasal and/or ocular changes. Individual body weights were recorded on days 1, 8 and 15. A gross pathological examination was conducted on all animals immediately following the last exposure of the study. The brain, kidneys, lungs, liver, spleen, adrenals, ovaries and testes were dissected free of fat and weighed. Histopathological examination of selected organs was conducted.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
> 246 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 246 ppm = 1875 mg/m3; no mortality or treatment-related effects at any exposure concentration
No mortality occurred and no treatment-related toxic effects were observed in any of the test group animals.
Clinical signs:
other: There were no clinical signs.
Body weight:
There were no significant differences in group mean body weights between exposed and control animals at any time period throughout the study.
Gross pathology:
Organ weight data analysed by the Welch Trend test indicated a dose-dependent increase in female spleen weight. This increase was statistically significant in the 250 ppm exposure group when expressed as an absolute weight or as a percentage of body weight. A statistically significant increase in relative liver weight was also observed in females exposed to 250 ppm when compared with controls. No other statistically significant changes in organ weights were observed in females. The spleen and liver weight increases observed in females is of questionable toxicological significance because of the magnitude of the changes and the lack of correlation with histopathological or male data. No treatment-related changes were evident at necropsy. Histopathological examination did not reveal treatment-related effects in any tissues or organs. The changes noted in tissues of these rats were considered to be typical of incidental findings in rats of this age and strain euthanised in this manner.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
In a 2-week vapour inhalation study, conducted to GLP and following a protocol similar to that in OECD guideline 412 but with significant deviations, there were no adverse effects in rats exposed to 1,1,3,3-tetramethyl-1,3-divinyldisiloxane at concentrations of 5, 50 or 246 ppm. An NOAEC of >=246 ppm (1875 mg/m3, equivalent to 1.9 mg/l) was determined.