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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2c The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trimethoxysilane (Silane 51-26)
No further details provided

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
No data
Doses:
4.0, 8.0, and 16.0 ml/kg bw
No. of animals per sex per dose:
4/sex/dose at the  highest dose tested and 5/sex/dose at the two lower doses
Control animals:
no
Details on study design:
The test material was administered by dermal application (under occlusive cover) to three groups of rabbits (4/sex/dose at the  highest 
dose tested and 5/sex/dose at the two lower doses). The animals  were observed for mortality and toxic effects immediately after dosing  
and daily for a total of 14 days.  At the end of the 14 day observation  period the surviving animals were weighed, sacrificed and necropsied.   
Animals that died during the study were also subjected to a necropsy.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
7.46 mL/kg bw
95% CL:
>= 5.05 - <= 11.04
Sex:
female
Dose descriptor:
LD50
Effect level:
6.73 mL/kg bw
95% CL:
>= 3.79 - <= 11.94
Mortality:
See detail below
Clinical signs:
See detail below
Body weight:
See detail below
Gross pathology:
See detail below
Other findings:
Local cutaneous effects included erythema, edema, necrosis, ecchymosis, fissuring (in one), ulceration, desquamation, scabs and alopecia.

Any other information on results incl. tables

Sluggishness, salivation (in 2), prostration, emaciation and a clear or red discharge around nose (of 2) were among the signs of toxicity observed.  Time to death for most animals ranged from one to 6 days.  One male died at 2 hours.  One affected survivor recovered at 14 days.  Gross pathological findings included bright or dark red lungs, tan to red raised nodules or foci on the lungs, lungs of one with necrotic areas, tan livers, liquid-filled (in one) and intestines (in one) hemorrhaged, white or black foci on stomachs or intestines, cream-colored foci on intestines of one, one with mottled and dark red kidneys and a tan raised mass on the kidney of one.

A few lungs that had tan nodules were subjected to histopathologic evaluation.  These included lungs from 2 males receiving 4.0 ml/kg of test material and one female receiving 8.0 ml/kg.  In addition, a kidney from a female dosed with 4.0 ml/kg was evaluated.  Grossly, this kidney exhibited a tan mass.  Histopathology of the lungs included abscesses, congestion, hemorrhages, edema, alveolar histiocytosis, mononuclear cells and black deposits.  The kidney was found to have interstitial and tubular nephritis resulting from a protozoan infection.

MALES:
Dosage (ml/kg): 16.0
Dead/Dosed: 4/4 (insufficient sample was available for
dosing in the usual 5 animals at this dose level; 5/5
mortality ratio assumed for LD50 determination).
Days to Death: 0, 1, 1, 1
Mean Weight, g +/- S.D.:
0 days: 2423 +/- 167
7 days: -
14 days: -
Skin Irritation: Erythema, edema, ecchymosis, necrosis at
death 
Signs of Toxicity: Prostration at 1 hr; clear to red
discharge on perinasal area of 2 at death. Death of 1 at 2
hr.
Gross Pathology: Lungs dark or bright red; livers tan;
stomach of 1 with white foci, lined with pus.

Dosage (ml/kg): 8.0
Dead/Dosed: 3/5
Days to Death: 3, 3, 5
Mean Weight, g +/- S.D.:
0 days: 2333 +/- 73
7 days: 1862 +/- 5
14 days: 1784 +/- 183
Skin Irritation: Erythema, edema, ecchymosis, necrosis at 1
day to death or 14 days; ulceration at death or 14 days;
alopecia of 2 at 7 to 14 days; scabs, desquamation on 2 at
14 days.
Signs of Toxicity: Sluggishness at 1 day; salivation in 1 at
death (3 days); emaciation at death or 7 days; prostration
in 1 at 7 days. 
Gross Pathology: In animals that died, lungs dark red; lungs
of 1 with cream-colored foci and necrotic areas; liver of 1
tan; stomach of 1 with black foci; stomach of 1
liquid-filled; intestines hemorrhaged or with white areas.
In survivors, lungs dark red; lungs dark red; lungs of 1
with raised cream-colored areas. 

Dosage (ml/kg): 4.0
Dead/Dosed: 0/5
Days to Death: 
Mean Weight, g +/- S.D.:
0 days: 2709 +/- 236
7 days: 2436 +/- 193
14 days: 2614 +/- 239
Skin Irritation: Erythema, ecchymosis at 1 day; edema at 1
to 14 days; desquamation, necrosis, ulceration, scabs,
alopecia at 7 to 14 days.
Signs of Toxicity: Emaciation in 1 at 7 days.  Recovery at
14 days. 
Gross Pathology: Lungs with raised cream-colored areas or
dark red foci (lungs of 2 examined microscopically). 

FEMALES:
Dosage (ml/kg): 16.0
Dead/Dosed: 4/4 (insufficient sample was available for
dosing in the usual 5 animals at this dose level; 5/5
mortality ratio assumed for LD50 determination).
Days to Death: 1, 1, 1, 1
Mean Weight, g +/- S.D.:
0 days: 2309 +/- 62
7 days: -
14 days: -
Skin Irritation: Erythema, edema, ecchymosis, necrosis at
death
Signs of Toxicity: Prostration at 1 hr; oscillation of eyes
of 1 at 1 hr; salivation in 1 at death.
Gross Pathology: Lungs bright to dark red; livers tan;
stomachs of 2 with black foci; stomach lining of 1
hemorrhaged; kidneys of 1 mottled dark red.

Dosage (ml/kg): 8.0
Dead/Dosed: 3/5
Days to Death: 3, 3, 6
Mean Weight, g +/- S.D.:
0 days: 2402 +/- 65
7 days: 1930 +/- 156
14 days: 1966 +/- 385
Skin Irritation: Erythema, ecchymosis at 1 day persisting on
2 to death; edema, necrosis at 1 to 14 days or death;
desquamation on 2 at 7 to 14 days or death; ulceration on 2
at 7 to 14 days; scabs on 1 at 14 days; alopecia of 1 at 14
days.
Signs of Toxicity: Sluggishness at 1 day; prostration in 1
at 1 day; emaciation at 7 to 14 days or death. 
Gross Pathology: In animals that died, lungs bright to dark
red; lungs of 1 with cream-colored foci; intestines with
white or cream-colored foci; stomach of 1 liquid-filled.  In
survivors, lungs with cream-colored nodules (lungs of 1
examined microscopically); lungs of 1 dark red. 

Dosage (ml/kg): 4.0
Dead/Dosed: 1/5
Days to Death: 4 
Mean Weight, g +/- S.D.:
0 days: 2564 +/- 66
7 days: 2380 +/- 215
14 days: 2530 +/- 183
Skin Irritation: Erythema at 1 day; edema, necrosis at 1 to
14 days; ecchymosis on 2 at 1 day or death; fissuring on 1
at 7 days; ulceration at 7 days or death; scabs, alopecia,
desquamation (on 2) at 7 to 14 days.
Signs of Toxicity: Sluggishness in 1 at 1 day. 
Gross Pathology: In animal that died, lungs bright to dark
red.  In survivors, lungs of 2 dark red; kidney of 1 with a
raised, cream-colored mass (examined microscopically).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study (reliability score 2) conducted using a protocol comparable to OECD 402 (no data on GLP), the LD50 for trimethoxysilane was 7.46 ml/kg bw in male rabbits and 6.73 ml/kg bw in female rabbits.
Executive summary:

In an acute dermal toxicity study (reliability score 2) conducted using a protocol comparable to OECD 402 (no data on GLP), trimethoxysilane was administered under an occlusive dressing to the skin of rabbits at doses of 4.0, 8.0, and 16.0 ml/kg bw (4/sex/dose at the highest dose tested and 5/sex/dose at the two lower doses). The LD50 was 7.46 ml/kg bw in male rabbits and 6.73 ml/kg bw in female rabbits. Local cutaneous effects included erythema, oedema, necrosis, echymosis, fissuing (one animal), ulceration, desquamation, scabs and alopecia. Sluggishness, salivation, prostration, emaciation, and a clear or red discharge around the nose were among the clinical findings. Gross pathological findings included bright or dark red lungs, tan to red raised nodules or foci on the lungs, lungs of one with necrotic areas, tan livers, liquid-filled haemorrhaged intestines, white or black foci on stomach or intestines, cream coloured foci on intestines, one with mottled and dark red kidneys and one with tan raised mass on kidney. Histopathology of lungs with tan nodules showed abscesses, congestion, haemorrhages, oedema, alveolar hystiocytosis, mononuclear cells and black deposits. Histopathology of the kidney with raised mass showed effect due to protoaxan infection.