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Toxicological information

Acute Toxicity: oral

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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

Constituent 1
Chemical structure
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 levelsopen allclose all
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
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
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.