2,11-Dioxa-3,10-disiladodecane, 3,3,10,10-tetramethoxy-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test conducted in accordance with generally accepted scientific standards, described in sufficient detail and with GLP, but limited compared to a standard guideline study since the study was terminate 5 hours after dosing.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study design was not based on a specific guideline. Its aim was to determine the systemic availability of 1,6- bis(trimethoxysilyl)hexane (test article and/or its derivatives) in rats following a single gavage dose.

GLP compliance:

yes

Test type:

other: non-guideline multi-dose acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

87135-01-1

Molecular formula:

C12H30O6Si2

Constituent 2

Reference substance name:

3,3,10,10-tetramethoxy-2,11-dioxa-3,10-disiladodecane

EC Number:

617-969-6

Cas Number:

87135-01-1

Molecular formula:

(CH3O)3Si(CH2)6Si(OCH3)3 C12 H30 O6 Si2

IUPAC Name:

3,3,10,10-tetramethoxy-2,11-dioxa-3,10-disiladodecane

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not stated
- Age at study initiation: 8 wk
- Weight at study initiation: 244-272 (m); 169-207 (f)
- Fasting period before study:
- Housing: 2/suspended wire mesh cage
- Individual metabolism cages: yes/no
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2-21.7
- Humidity (%): 41-63
- Air changes (per hr): 14.5 or 15.6 depending on room
- Photoperiod (hrs dark / hrs light):12 h/12/ h

IN-LIFE DATES: for main study From: 2009-10-19 To: 2009-10-20

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Each dosing solution was prepared individually: 125 mg/ml, 250 mg/ml, 500 mg/ml.
- Justification for choice of vehicle: none given

MAXIMUM DOSE VOLUME APPLIED: 4 mg/kg bw

DOSAGE PREPARATION: Each dosing solution was prepared individually: 125 mg/ml, 250 mg/ml, 500 mg/ml. Dosing solutions were not analysed.
The dosing solutions for the definitive study were prepared three days prior to experimental start and stored at room temperature.

HOMOGENEITY AND STABILITY OF TEST MATERIAL: No details.

Doses:

0, 500, 1000, 2000 mg/kg bw

No. of animals per sex per dose:

8 (4 each for blood sampling at 2h and 5h post-dosing)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: observation for survival only to 5 hours post dosing.
- Other examinations performed: none
- Blood samples taken at 2 h and 5 h after dosing for analysis of total silicon (see below).

Inductively coupled plasma-optical emission spectroscopy (ICP-OES) was used to determine the total silicon content in plasma rather than selecting for a specific derivative molecular species. The limit of quantitation was 4.8 µg equivalents of 1,6-bis(TMS)H/g plasma. The total silicon content detected in the plasma samples was significantly above the limit of quantitation for all dose groups at both blood collection time points, approximately two and five hours post dose administration. The group means and standard error of the mean were reported.

Statistics:

Standard error of means only.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

other: survival to 5 hours after treatment

Effect level:

2 000 mg/kg bw

Remarks on result:

other: non-standard acute study

Mortality:

0/16 deaths during 5 hours after treatment at 2000 mg/kg bw.

Clinical signs:

other: not recorded

Gross pathology:

not examined

Other findings:

Blood silicon - see table 1.

Any other information on results incl. tables

Table 1: Observed silicon concentration (mg equivalents of 1,6-bis(trimethoxysilyl)hexane

Approximate time after dose administration	Dose level (mg/kg bw)	Males	Females
2h	0	<LOQ	<LOQ
	500	65.3 +/-5.3	35.3 +/-4.4
	1000	113.4 +/-11.3	73.2 +/-13.4
	2000	235.3+/-43.7	130.2 +/-21.4
5h	0	<LOQ	<LOQ
	500	10.8 +/-1.0	15.2 +/-1.6
	1000	24.1 +/-2.8	32.7 -/-2.3
	2000	35.9 +/-3.2	25.6 +/-0.9

LOQ: limit of quantitation – 4.8 mg equivalents of 1,6-bis(trimethoxysilyl)hexane

Applicant's summary and conclusion

Interpretation of results:

other: cannot classify based on the data presented

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A well reported non-guideline study conducted according to GLP found that single oral doses of the test substance given to male and female rats caused no treatment-related mortality up to 5 hours after dosing despite the systemic availability of the test substance and/or its derivatives in the blood.