Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 Feb 1996 - 28 June 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Silquest Y-11542, gamma-ureidopropyltrimethoxysilane
- Physical state: clear, colorless, slightly viscous liquid
- Lot/batch No.: 2131UG060495
- Expiration date of the lot/batch:
- Specific gravity: 1.14 glml, as determined by WIL Research Laboratories, Inc. pharmacy personnel)
- Storage conditions: original container at room temperature
- Stability under test and storage conditions: Test material stability data are the responsibility of
the Sponsor. Under the conditions employed during the testing of this material, the Sponsor has indicated that the material is stable, provided the sample is not contaminated, is properly sealed, and stored under normal conditions as dictated by good manufacturing practice.

Test animals

Species:
rat
Strain:
other: Albino rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl:CD BR
- Source: Charles River Breeding Laboratories, Inc. Portage, MI, USA
- Age at study initiation: young adult
- Weight at study initiation: 231-300 g
- Fasting period before study: 18-20 h prior to dosing
- Housing: Individual in suspended wire-mesh cages
- Diet: Purim@ Certified Rodent Chow@ #5002, ad libitum. Analysis of feed was performed and provided by the manufacturer.
- Water: municipal water, ad libitum. Water was analysed in accordance with Standard Operating Procedures.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0-22.3 (71.6-72.1 °F)
- Humidity (%): 43.7-50.0
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.39 ml/kg bw

DOSAGE PREPARATION:
A sufficient amount of test material was transferred from the original container to a labeled storage vessel. A stir bar was added, and the test material was maintained on a magnetic stir plate prior to dispensation and throughout the dosing procedure.

RATIONALE FOR DOSE SELECTION:
Prior to initiation of the main study, a range-finding study was conducted in which groups of one male and one female rat were dosed at levels of 500, 1000, 2000, 3500 and 5000 mg/kg bw. There were no deaths during the range-finding study. Based on these results, 5000 mglkg was selected as the first level on the main study.
Doses:
Range-finding test: 500, 1000, 2000, 3500 and 5000 mg/kg bw
Main study: 5000 mg/kg bw
No. of animals per sex per dose:
Range-finding test: 1
Main study: 5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The rats were observed at approximately 1.0, 3.0 and 4.0 hours post-dose on Day 0 and twice daily (morning and afternoon) thereafter for 14 days.
- Frequency of weighing: Body weights were obtained and recorded on study days -1, 0 (initiation), 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and gross pathology (major organ systems of the cranial, thoracic and abdominal cavities for all animals)

Results and discussion

Preliminary study:
There were no deaths during the range-finding study. Based on these results, 5000 mg/kg bw was selected as the first level on the main study.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
There were no deaths during the study.
Clinical signs:
Three rats had wet and/or dried yellow urogenital staining. Yellow urogenital staining is a common, non-specific finding in acute studies that, in isolation, is not evidence of significant toxicity. Clear ocular discharge and mucoid feces were noted for one female animal. There were no other clinical findings. All animals appeared normal by day 3 or earlier and throughout the remainder of the study.
Body weight:
There were no remarkable changes or differences in body weights.
Gross pathology:
At the terminal necropsy, dark red lungs were noted for three rats. This finding was not considered to be test material-related as it is often noted in animals that have been euthanised by carbon dioxide inhalation. There were no other gross necropsy findings.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test material was investigated for acute oral toxicity according to the OECD TG 401, and in compliance with GLP. The undiluted test material was administered once via oral gavage to 5 Crl:CD BR rats per sex at a dose of 5000 mg/kg bw. No mortality occurred and clinical signs were only noted in one female (reversible within 3 days) throughout the study period. Based on these findings, classification for acute oral toxicity according to Regulation (EC) No 1272/2008 is not warranted.