2-Propenoic acid, 2-methyl-, tris(1-methylethyl)silyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August to 29 August 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recent study conducted by a GLP certified laboratory in accordance with a suitable study guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

EC Number:

700-182-8

Cas Number:

134652-60-1

Molecular formula:

C13 H26 O2 Si

IUPAC Name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

Details on test material:

- Name of test material (as cited in study report): TIS-M
- Lot/batch No.: 3301 MS-0505-4
- Storage condition of test material: Under nitrogen at room temperature, in the dark.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: The bodyweights fell within an interval of +/- 20% of the mean initial bodyweight of the first treated group.
- Fasting period before study: Overnight. There was also a 3 to 4 hour fasting period after dosing.
- Housing: Animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: Certified Rat and Mouse Diet (Code 5LF2) Supplied by BCM IPS Limited, London, UK; ad libitum.
- Water: Mains drinking water; ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15.
- Photoperiod: 12 hours light: 6am-6pm

IN-LIFE DATES: From: 9 August 2005 To: 23 August 2005.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Method:
A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a further group of three fasted females at the same dose level. The test material was administered orally undiluted. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. Clinical signs and bodyweight development were monitored during the study.

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examiniation of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Doses:

One dose applied: 2000mg/kg.

No. of animals per sex per dose:

3 initial at 2000 mg/kg
3 additional at 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations made after 30mins, 1hr, 2hrs and 4hrs on the day of dosing (day 0); daily from days 1-14 and weighings made on days 7 and 14 (weekly), as well as prior to dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

Signs of systematic toxicity noted during the study were hunched posture, lethargy, ataxia and decreased respiratory rate. one animal appeared normal throughout the study and the reaming five animals appeared normal one or two days after dosing.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Evaluation of Data:

Data evaluations included the relationship, if any, between the exposure of animal to the test material and the incidence and severity of all abnormalities including behavourial and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD₅₀) of the test material was made: > 2500 mg/kg bodyweight.

Table 1: Mortality Data:

Dose Level m/kg	Sex	Number of Animals treated	Deaths During Day of Dosing (Hours)				Deaths During Period After Dosing (Days)								Deaths
			½	1	2	4	1	2	3	4	5	6	7	8-14
2000	Female Female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
		3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

Table 2: Individual Clinical Observations:

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-1 Female	0	0	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Female	HA Rd	HLA Rd	HLA Rd	HA Rd	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	HA	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	HRd	HA Rd	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = No signs of systemic toxicity

A = Ataxia

H = Hunched posture

L = Lethargy

Rd = Decreased respiratory rate Table 3: Individual Bodyweights and Weekly Bodyweight Changes:

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	221	253	269	32	16
	1-1 Female	223	243	269	20	26
	1-2 Female	223	254	268	31	14
	2-0 Female	233	266	280	33	14
	2-1 Female	228	265	280	37	15
	2-2 Female	238	262	275	24	13

Table 4: Individual Necropsy Findings:

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Female	Killed Day 14	No Abnormalities Detected
	1-1 Female	Killed Day 14	No Abnormalities Detected
	1-2 Female	Killed Day 14	No Abnormalities Detected
	2-0 Female	Killed Day 14	No Abnormalities Detected
	2-1 Female	Killed Day 14	No Abnormalities Detected
	2-2 Female	Killed Day 14	No Abnormalities Detected

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the registered substance in the female Sprague-Dawley CD strain rat was estimated to be greater than 2500mg/kg bodyweight (GHS Category 5 >2000 - 5000 mg/kg bodyweight). However, in accordance with CLP criteria, the substance is not classified, as it does not fall within the definitions of Categories 1 to 4.

Executive summary:

An acute oral toxicity study of the substance was carried out according to OECD Guideline 423 using Sprague-Dawley CD Strain rats. The registered substance was applied undiluted and by gavage, and after 14 days it was determined that the acute oral median lethal dose (LD₅₀) was greater than 2500 mg/kg/bw. The registered substance was classified as being in GHS Category 5 (>2000 - 5000 mg/kg bodyweight). However, in accordance with CLP criteria, the substance is not classified, as it does not fall within the definitions of Categories 1 to 4.