Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 October 2011 to 08 November 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): (Chloromethyl)triethoxysilane
- Physical state: colourless liquid
- Density: 1.048 g/ml (at 20 °C, 1013 hPa)
- Lot/batch No.: KH09731
- Expiration date of the lot/batch: 01 August 2020
- Storage condition of test material: at room temperature (20±5 °C) and protected from light

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Rat, RccHan: WIST(SPF)
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, The Netherlands
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 171.9 g–197.8 g
- Fasting period before study: overnight fasting period prior to treatment and approximately 3 hours post dose
- Housing: In groups of up to five in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH&CoKG, 73494 Rosenberg, Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst, Switzerland). Paper enrichment, batch no. 75, (Enviro-dri from Lillico Biotechnology, Surrey, UK) was included.
- Diet: Pelleted Harlan Teklad 2914C rodent maintenance diet (batch no. 46/11, Provimi Kliba AG, 4303 Kaiseraugst, Switzerland), ad libitum
- Water: Community tap water from Itingen, ad libitum
- Acclimation period: 5-12 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: 18 October 2011 to: 08 November 2011

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.94 ml/kg bw at the 2000 mg/ kg bw dose level
Doses:
sighting study: 300 and 2000 mg/kg bw
main study : 2000 mg/kg bw
No. of animals per sex per dose:
sighting study: 1 female at 300 mg/kg and 1 female at 2000 mg/kg
main study: 4 females at 2000 mg/kg
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2-15
- Frequency of weighing: day 1 (prior to administration) and on test days 8 and 15
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
The sighting study started with a single female at a dose of 300 mg/kg body weight. As no clinical signs were observed at the initial dose, the next higher dose level of 2000 mg/kg investigated, using a single female. As no mortality occurred at 2000 mg/kg, the sighting study was complete and the main study was conducted at 2000 mg/kg.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal treated at 2000 mg/kg was found dead on test day 2. All other animals survived the scheduled treatment and observation periods.
Clinical signs:
In animal no. 1 treated at 300 mg/kg, decreased activity, hunched posture and ruffled fur were noted on test day 1. Thereafter, the animal was free of clinical signs up to the end of the observation period. In the animals treated at 2000 mg/kg, dragging of limbs, decreased activity, hunched posture, ruffled fur and / or swaying gait were noted on test day 1 and persisted up to test day 3 at the latest. Thereafter, no clinical signs were noted up to test day 15, the end of the observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
In animal no. 6 which died spontaneously, distended stomach was recorded at necropsy. No abnormal macroscopic findings were recorded in the remaining animals at scheduled necropsy.

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 item was tested for acute oral toxicity according to the OECD TG 420, and in compliance with GLP. In the main study one animal treated at 2000 mg/kg was found dead on test day 2. All other animals survived the scheduled treatment and observation periods. The clinical signs recorded at this dose level were dragging of limbs, decreased activity, hunched posture, ruffled fur and/or swaying gait on test day 1 and persisted up to test day 3 at the latest. Based on Annex 3 and 4 of the OECD TG 420, the test item is classified as GHS category 5 corresponding to 2000 mg/kg body weight < LD50 (female rat) < 5000 mg/kgbw. Classification for acute oral toxicty according to EC/1272/2008 is not warranted.