4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 16 April 1999 to 28 May 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

EC Number:

240-212-2

EC Name:

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Cas Number:

16068-37-4

Molecular formula:

C14H34O6Si2

IUPAC Name:

4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane

Test animals

Species:

rat

Strain:

other: Crl:CD (SD) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Labs, Raleigh, NC, USA
- Age at study initiation: 8-10 wk (m); 9-11 wk (f)
- Weight at study initiation, g: 246-313 (m); 193-216 (f)
- Fasting period before study: 18-20 h
- Housing: 1/suspended wire mesh cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 71.5-72.2 deg F
- Humidity (%): 39-57.7
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: not given

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
None

MAXIMUM DOSE VOLUME APPLIED: 0.26 ml/kg bw (neat test substance)

Doses:

150, 200, 250 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 21 days
- Frequency of observations and weighing: mortality hourly to 4 h, then twice daily for 21 days; clinical observations hourly to 4 h, then daily for 21 days; body weights at -1, 0, 7, 14 and 21 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Statistics:

Litchfield & Wilcoxon

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

153 mg/kg bw

Based on:

test mat.

95% CL:

140 - 166

Remarks on result:

other: Adverse effects observed

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

170 mg/kg bw

Based on:

test mat.

95% CL:

134 - 215

Remarks on result:

other: Adverse effects observed

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

161 mg/kg bw

Based on:

test mat.

95% CL:

139 - 185

Remarks on result:

other: Adverse effects observed

Mortality:

3 out of 10 animals (2 male and 1 female rats) treated with 150 mg/kg bw died between days 5 and 9 of the study period. All animals treated with 200 mg/kg bw died within 9 days of the observation period. 9 out of 10 animals (5 male and 4 female rats) treated with 250 mg/kg bw died during the treatment period. 8 of these animals died within the first 9 days post-administration, while 1 animal died later (after day 9).

Clinical signs:

other: There were clinical findings in all dose groups, most (4/5 or 5/5) had decreased defaecation, over a third were hypoactive, had pale extremities, impaired muscle coordination or hypothermia. Many had discharge from the eyes, nose or anogenital area. At th

Gross pathology:

The target organ was identified as the liver, with hepatic findings in 24 of the 30 (80%) of the animals in the study (17/22) that died and 7/8 that survived). Other observations on gross necropsy of those that succumbed were: red fluid contents in the abdominal cavity, thoracic cavity and/or urinary bladder; dark red stomach and/or intestinal contents; lungs that were dark red or pale; discoloured thymus; pale pancreas; foamy contents in the trachea; reddened testes and/or reddened and enlarged mediastinal lymph nodes. The scheduled necropsy found (besides the hepatic effects) white areas or capsular scarring on the spleen; dark red areas on the lungs.

Any other information on results incl. tables

Table 1: Number of animals dead and time range within which mortality occurred

Dose (mg/kg bw)	Mortality (dead/total)			Time range of deaths (days)
	Male	Female	Combined	1-4	5-9	10-21
150	2/5	1/5	3/10	-	3	-
200	5/5	5/5	10/10	1	9	-
250	5/5	4/5	9/10	-	8	1

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

A reliable study conducted in compliance with the standard guideline and in accordance with GLP, identified LD50 values of 153 and 170 mg/kg bw for male and female rats for 4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane, respectively. The liver was found to be the target organ and there was clear evidence of toxicity at the lowest tested dose of 150 mg/kg bw.