Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
11.05.1992 to 27.05.1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
Version / remarks:
(Note: 1981 version was applicable at time of study; subsequently superseded by 2009 version)
Deviations:
yes
Remarks:
(exposure only for 14-days; no clinical pathology)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
10 days over two weeks
Frequency of treatment:
6 hours/days, 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
5 ppm (analytical)
Dose / conc.:
50 ppm (analytical)
Dose / conc.:
246 ppm (analytical)
Remarks:
250 ppm (target)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
No treatment-related toxic effects were observed in any of the test group animals.
Mortality:
no mortality observed
Description (incidence):
No mortality occurred.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no significant differences in group mean body weights between exposed and control animals at any time period throughout the study.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
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.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No treatment-related changes were evident at necropsy.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
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.
Histopathological findings: neoplastic:
not examined

Effect levels

Dose descriptor:
NOAEC
Effect level:
>= 246 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: 246 ppm = 1875 mg/m3; no mortality or treatment-related effects at any exposure concentration

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
In a 2-week vapour inhalation study, conducted according to a protocol similar to OECD Test Guideline 412 but with significant deviations and in compliance with GLP, 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. A NOAEC of >=246 ppm (1875 mg/m3) was determined.
Executive summary:

In a GLP study, conducted using a protocol similar to OECD guideline 412 (subacute inhalation toxicity: 28 -day study), the inhalation toxicity of 1,1,3,3-tetramethyl-1,3-divinyldisiloxane was evaluated in rats exposed for 2 weeks.

Groups of 10 male and 10 female Sprague Dawley rats were exposed 6 hours/day, 5 days/week for 2 weeks to 0, 5, 50 and 250 ppm (target conceentrations; analytical concentrations were 0, 5, 50 and 246 ppm) Dow Corning 4-2776 fluid. Animals were observed for treatment-related signs of toxicity, growth and mortality, sacrificed after 2 weeks and examined for changes in organ weights, gross pathology and histopathology.

No gross effects, mortality or clinical signs of toxicity were observed which were considered to be treatment-related. At 246 ppm, a significant increase in liver and spleen weight was observed in female rats but histopathological examination did not reveal any lesions that correlated with the increased organ weights. Microscopic examination of the respiratory tract and selected organs did not reveal any toxicologically-significant changes.

Under the conditions of this study, a NOAEC of >=246 ppm (1875 mg/m3), the highest concentration tested, was determined for 1,1,3,3-tetramethyl-1,3-divinyldisiloxane in rats.