N-(3-{1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]trisiloxan-3-yl}propyl)prop-2-enamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-10-26 to 2010-01-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP study according to OECD technical guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate attached to the report

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-(3-{1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]trisiloxan-3-yl}propyl)prop-2-enamide

EC Number:

700-253-3

Cas Number:

115258-10-1

Molecular formula:

C15H37NO4Si4

IUPAC Name:

N-(3-{1,1,1,5,5,5-hexamethyl-3-[(trimethylsilyl)oxy]trisiloxan-3-yl}propyl)prop-2-enamide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
- Age at study initiation: 8 weeks
- Weight at study initiation: 188g - 210g
- Fasting period before study: Food was removed on D-1 and then redistributed 4 hrs after the test item administration
- Housing: by groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contained sawdust bedding which was changes at least 2 times a weel. Each cage was installed in conventional air conditioned animal husbandry
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 (07.00h - 19.00h)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

- 2 grammes of the test item were dissolved in DMSO (Sigmna, Batch-No. 038K0710)
- the preparation was a homogenous and colourless solution
- DMSO was used as a vehicle, because the test item was not soluble in water (tested firstly)
- the animals received an effective dose of 2000mg/kg body weight of the test item under a volume of 10mL/kg body
- the solution was administered by gavage using a syringe graduated fitted with an oesophageal metan canula

Doses:

2000mg/kg boda weight

No. of animals per sex per dose:

6 (in two subsequently tested groups of three rats each)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

A) DAILY EXAMINATIONS:
- Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions
- Observation focuses mainly on presence or absence of symptoms listed in the attached table 1a (1b for abbreviations)
- Mortality report

B) PERIODICAL EXAMINATIONS:
- animals were weighed on day 0 (prior to the study), then on day 2, day 7, and day 14
- weight changes were calculated and recorded

C) EXAMINATION AT THE END OF THE TEST:
- on day 14, the animals were anaesthesised with Na-pentobarbital, with subsequent administration to fatal levels
- macroscopic observations were entered on individual autopsy sheets
- organs, likely to be modified in cases of acute toxicity were examined

Statistics:

Not applicable in present study

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: No mortalities up to limit dose of 2000mg/kg bw

Mortality:

No mortalities

Clinical signs:

See Table 1a (and 1b for explanations)
- increased salivation in some animals on the first day of the study
- one animal: decrease in spontaneous activity and in righting reflex, dyspnea and piloerection
- all animals recovered a normal behaviour 24 hrs post-dose

Body weight:

See Table 2
- a slight decrease in body weight gain was noted on day 2 compared to day 0 (-3.5%, mean of 6 animals)
- normal body weight evolution on day 7

Gross pathology:

See Table 3
- in three animals: thickness of the forestomach at the end of the study

Any other information on results incl. tables

Please see attached tables

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In accordance with the Globally Harmonized System (Regulation (EC) No 1272/2008), the test item is not to be classified. No signal word and hazard statement are required.

Executive summary:

The test item N-[3 -tris(trimethylsilyloxy)silylpropyl]prop-2 -enamide was administered by oral route to a group of 6 female Sprague Dawley rats at the single dose of 2000 mg/kg body weight. The experimental protocol was established on the basis of the official method as defined in the O.E.C.D.guideline N° 423 dated December 17^th, 2001 and the test method B. 1ter of the Council regulation No440/2008.

No mortality occurred during the study.

An increased salivation was noted in three animals (3/6) on the first day of the study. A decrease inspontaneous activity and in righting reflex, a dyspnea and piloerection were also noted in one animal(1/6). The animals recovered a normal behaviour at 24 hours post-dose.

A slight decrease in body weight was noted on day 2 compared to day 0 (-3.5% - mean for 6 animals). The animals recovered a normal body weight evolution on day 7 and a normal body weight on day 14.

The macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

In conclusion, the LD50 of the test item N-[3 -tris(trimethylsilyloxy)silylpropyl]prop-2 -enamide is higher than 2000 mg/kg body weight by oral route in the rat.

According to the criteria for classification, packaging and labelling of dangerous substances and preparations in accordance with the E.E.C. Directives 67/548, 2001/59 and 99/45, the test item N-[3 -tris(trimethylsilyloxy)silylpropyl]prop-2 -enamide is not to be classified. No symbol and risk phrase are required.

In accordance with the Globally Harmonized System (Regulation (EC) No 1272/2008), the test item is not to be classified. No signal word and hazard statement are required.