Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 November 1986 to 14 August 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Guideline (84/449/EEC)
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): Si 264 (3-Thiocyanatopropyltriethoxysilane)
- Substance type: no data
- Physical state: light yellow liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: Wi 12083
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: room temperature
- Other: Solubility: Well soluble in organic solvents; hardly soluble in water

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: 49 to 56 days (males), 63 to 72 days (females)
- Weight at study initiation: 130 to 196 g (males), 132 to 161 g (females)
- Fasting period before study: 16 h
- Housing: singly in Macrolon cages type II
- Diet (e.g. ad libitum): standard diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 November 1986 To: 18 December 1986

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 215, 316, 464 or 681 mg/ml
- Amount of vehicle (if gavage): 2.15 or 3.16 ml/kg bw (3.16 ml/kg bw given to top dose females only)
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 3.16 ml/kg
Doses:
464, 681, 1000, 1470 mg/kg bw (males and females), 2150 mg/kg bw (females only)
No. of animals per sex per dose:
generally 5 (10 females given 1000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were observed "for the first four to 8 hours" (apparently at 0.5, 1, 2, 4 and 8 h) for mortality or clinical signs of toxicity. Animals were then checked for mortality twice daily (only once on weekends and national holidays). For clinical signs of toxicity, animals were observed once daily. Body weights were recorded at the start of the study, and on days 7 and 14 after administration, or after death (provided that the animals survived one day)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 values and the slopes of the dose response curves were determined for each sex and for both sexes together by probit analysis with a 95% confidence interval.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 986 mg/kg bw
Based on:
test mat.
Remarks:
mortality
95% CL:
>= 658 - <= 2 180
Remarks on result:
other: mortality: 0/5 given 464 mg/kg bw, 2/5 given 681 mg/kg bw, 2/5 given 1000 mg/kg bw, 4/5 given 1470 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 650 mg/kg bw
Based on:
test mat.
Remarks:
mortality
95% CL:
>= 1 252 - <= 4 021
Remarks on result:
other: mortality: 1/5 given 464 mg/kg bw, 0/5 given 681 mg/kg bw, 2/10 given 1000 mg/kg bw, 1/5 given 1470 mg/kg bw, 4/5 given 2150 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 423 mg/kg bw
Based on:
test mat.
Remarks:
mortality
95% CL:
>= 2 049 - <= 3 478
Remarks on result:
other: mortality: 1/10 given 464 mg/kg bw, 2/10 given 681 mg/kg bw, 4/15 given 1000 mg/kg bw, 5/10 given 1470 mg/kg bw, 4/5 given 2150 mg/kg bw
Mortality:
0/5 males given 464 mg/kg bw died.
2/5 males given 681 mg/kg bw died (1 and 24 h after administration)
2/5 males given 1000 mg/kg bw died (1 and 2 h after administration)
4/5 males given 1470 mg/kg bw died (1, 1, 2 and 4 h after administration)

1/5 females given 464 mg/kg bw died (1 h after administration)
0/5 females given 681 mg/kg bw died
2/10 females given 1000 mg/kg bw died (both 2 h after administration)
1/5 females given 1470 mg/kg bw died (1 h after administration)
4/5 females given 2150 mg/kg bw died (one at 0.5 h, the rest 1 h after administration)
Clinical signs:
Signs of toxicity included: hypokinesia, clonic convulsions, decrease of muscle tone, salivation and strenuous breathing.
Stilted gait, tonic convulsion, ptosis, mydriasis, lacrimation, epistaxis, diarrhoea, cold extremities and vocalisation on handling occurred in individual animals.
Ante mortem general loss of reflexes and dyspnea were observed.
Symptoms of toxicity were observed 3 minutes after substance administration and generally lasted up to one day (epistaxis up to 4 days after administration).
Body weight:
No effects on body weight noted
Gross pathology:
Observations at necropsy included: tympany in the stomach, red stomach and intestinal mucous membranes, liquid-filled intestine, red discolouration in the intestine of individual animals, red spotted/marbled lung of emphysematous consistency, reddened peritoneum, pancreas, spleen and external skin in individual animals.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: no data

Any other information on results incl. tables

The slopes of the dose response curves were:

Males: 4.6 (95% CL 0.8 - 8.4)

Females: 5.1 (95% CL 1.2 - 9.0)

Males and females: 2.9 (95% CL 0.9 - 4 .9)

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a study performed in accordance with OECD Test Guideline 401 (acute oral toxicity), Si 264 (triethoxy(3-thiocyanatopropyl)silane) was harmful when administered via oral gavage to rats, with acute oral LD50s of 986 (male), 1650 (female) and 1423 mg/kg bw (males and females) calculated.
Executive summary:

An acute oral study was carried out according to OECD Test Guideline 401 (acute oral toxicity), in which male and female Wistar rats were exposed to Si 264 (triethoxy(3-thiocyanatopropyl)silane) via oral gavage.

 

Generally, groups of five males and five females were given a single oral gavage administration of Si 264 (in peanut oil) at 464, 681, 1000, 1470 or 2150 mg/kg bw, and observed for 14 days (ten females were given 1000 mg/kg bw, and no males were treated with 2150 mg/kg bw). After the observation period, surviving animals were sacrificed. Both sacrificed animals and those dying over the course of the experiment were subject to gross necropsy.

 

Overt signs of toxicity included hypokinesia (decreased body movement), clonic convulsions, decrease of muscle tone, salivation and strenuous breathing. Adverse effects on the stomach, intestines and lungs were noted at necropsy (the peritoneum, pancreas, spleen and skin were also affected in individual animals). There was no noted effect on body weight. Over the course of the study, mortality were observed in individuals belonging to each treatment group between 0.5 and 24 hours after administration.

 

Under the conditions of this study, Si 264 was harmful to rats. LD50 values were calculated for males (986 mg/kg bw), females (1650 mg/kg bw) and male and female animals (1423 mg/kg bw).