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Administrative data

Description of key information

The key acute oral toxicity study, conducted according to an appropriate guideline and in compliance with GLP, concluded an LD50 value of >5000 mg/kg bw for 1,1,3,3-tetramethyl-1,3-divinyldisiloxane (Dow Corning Corporation, 1987).

A 2-week vapour inhalation study, conducted according to a protocol similar to OECD Test Guideline 412 and in compliance with GLP, reports no adverse effects in rats exposed to 1,1,3,3-tetramethyl-1,3-divinyldisiloxane at concentrations of 5, 50 or 246 ppm for 6 hours. The LD50 is higher than the highest exposure concentration of 246 ppm, equivalent to 1.9 mg/l (Dow Corning Corporation, 1993).

In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the dermal route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and inhalation routes are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 September 1987 - 7 October 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
other: "OECD Short term and long term toxicology groups final report" adopted in May 1981
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, Michigan
- Age at study initiation: 'young'
- Weight at study initiation: 237 +/- 18 grams
- Fasting period before study: ca. 18 hours prior to administration of test material
- Housing: All rats were housed individually in conventional design stainless steel, wire mesh bottom cages.
- Diet: Purina Rodent Chow, ad libitum
- Water: ad libitum
- Acclimation period: 7 days

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5000 mg/kg
No. of animals per sex per dose:
5M, 5F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: All animals were weighed 24 hours, 7 and 14 days after administration of the test material. The animals were observed frequently on the first day of dosing and twice a day thereafter, at least 4 hours apart during weekdays. Individual observations for mortalities and behaviour or other reactions were made for each animal.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: A complete gross pathologic examination was performed on all rats at the termination of the study.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
No visible changes in animal behaviour or any signs of toxicity were observed.
Body weight:
No obvious effects on body weight gains were noted.
Gross pathology:
Terminal sacrifice of the animals did not reveal any gross pathological alterations in the organs and tissues examined.
Other findings:
None reported.
Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >5000 mg/kg was reported in a study carried out according to current guideline and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 412 (Repeated Dose Inhalation Toxicity: 28/14-Day)
Deviations:
yes
Remarks:
(exposure only for 14-days; no particle sizing data; no clinical pathology)
GLP compliance:
yes
Test type:
other: subacute
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- 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

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

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
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:
yes
Duration of exposure:
6 h
Remarks on duration:
5 days/week, 10 days over two weeks
Concentrations:
5, 50 or 246 ppmn (analytical)
5, 50 or 250 ppm (nominal)
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes
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.
Key result
Sex:
male/female
Dose descriptor:
LC50
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
Mortality:
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.
Interpretation of results:
GHS criteria not met
Conclusions:
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 900 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key acute oral toxicity study reported an LD50 value of >5000 mg/kg bw for 1,1,3,3-tetramethyl-1,3-divinyldisiloxane, which was determined in a reliable study carried out according to current guideline and in compliance with GLP (Dow Corning Corporation, 1987). There were no mortalities or clinical signs during the study period. No obvious effects on body weight gains were noted and the terminal sacrifice of the animals did not reveal any gross pathological alterations in the organs and tissues examined.

The key study for acute inhalation endpoint was a 2-week vapour inhalation study, which was conducted according to a protocol similar to OECD Test Guideline 412 and in compliance with GLP. The animals were exposed to 5, 50 or 246 ppm of vapour for 6 hours, 5 days a week for 10 days. There were no mortalities or treatment related toxic effect in any of the test animals. Since there were no treatment related deaths, the acute inhalation toxicity LC50 is concluded to be higher than the highest exposure concentration of 246 ppm, equivalent to 1.9 mg/l (Dow Corning Corporation, 1993).

Since the highest dose level tested in the key study was below guideline limit values for acute inhalation testing of vapours, a reliable study for HMDS (CAS 107-46-0) has been included as supporting information. During the 4-hour exposure some of the animals exposed to concentrations of 14,050 and 16,659 ppm test material experienced prostration and convulsions. Ataxia was also observed in the high exposure group. The primary clinical sign after the exposure was staining of the eyes and face; this was evident in some of the animals of the two higher exposure groups for the entire observation period. In animals that died, congestion and/or haemorrhage of various lobes of the lung were observed in males and females. Congestion of the lungs was also noted in one female from each of the two higher exposure groups at the final sacrifice of the animals that survived exposure. The potential target organ identified is the lung, however this material should not pose acute inhalation hazard, since the no effect level and LC50are significantly higher than the standard limit exposure of 20 mg/l. An acute inhalation LC50of 15,956 ppm was determined for male and female rats in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP (Dow Corning Corporation, 1997). This is equivalent to ca. 106 mg/l.



Justification for classification or non-classification

Based on the available information for 1,1,3,3-tetramethyl-1,3-divinyldisiloxane, no classification for acute toxicity is required according to Regulation (EC) No 1272/2008.