Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
not applicable

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Some minor deviations were noted but these did not have an impact on the overall conduct of the study
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Some minor deviations were noted but these did not have an impact on the overall conduct of the study
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Some minor deviations were noted but these did not have an impact on the overall conduct of the study
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: HES10108 (supplied as Dow Corning BY 16-122B
- Expiration date of the lot/batch: 25-August-2017 / Lot number 0008624816
- Purity test date: -14-April-2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 0°C -32 °C, protected from light. Do not store with strong
oxidising agents
- Stability under test conditions: the liquid test item was tested undiluted
- Solubility and stability of the test substance in the solvent/vehicle: not applicable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

Other
- Physical state - liquid
- Color - colorless
- Active components - 95%: 3-Methacryloxypropyltris {[tris(trimethylsiloxy) silyl]
ethyldimethylsiloxy} silane
- Purity - 99.3% (non-volatile content)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 week sold
- Weight at study initiation: Step 1 - 200 - 201 grams and Step 2 - 153 - 181 grams
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water,
municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least five days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

IN-LIFE DATES: From: 25-Aprill-2016 To: 25-April-2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required .
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 female rats/step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for 14 days after dosing for general clinical signs , morbidity and mortality. The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
not applicable

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 - 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
Under the conditions of the present study, a single oral application of the test item HES10108 to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of HES10108 after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): > 2000 5000 mg/kg bw
Mortality:
The test item showed no mortality and no other acute oral toxicity characteristics after a single dose administration
Clinical signs:
The test item showed no other acute oral toxicity characteristics after a single dose administration
Body weight:
None of the animals showed weight loss during the observation period
Gross pathology:
No specific findings were noted
Other findings:
not applicable

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, a single oral application of the test item HES10108 to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of HES1 01 08 after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): > 2000 5000 mg/kg body weight
Executive summary:

In this acute oral study (conducted according to OECD Guideline 423, OPPTS 870.1100 and EU Method B.1 (tris) and GLP), two groups, each of three female Wistar Crl: WI (Han) rats, were treated with the HES10108 (Dow Corning BY 16 -122B) by oral gavage administration at a dosage of 2000 mg/kg body weight, in a stepwise manner. The test item was administered undiluted according to body weight.

All animals survived until the end of the study without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Under the conditions of the present study, a single oral application of the test item HES10108 (Dow Corning By 16 -122B) to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of HES1 0108 after a single oral administration to female rats, observed over a period of 14 days was:

L050 cut-off (rat): > 2000 -5000 mg/kg bw