Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4th October 2002 to 25th October 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
The test material was evaluated following a single oral administration to male and female Slc:SD rats. The oral route and a single dose of 2000 mg/kg were selected. According to the OECD Guidelines for acute toxicity studies, no further dose levels are necessary when there are no toxic signs at 2000 mg/kg.
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction mass of 3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-2-hydroxypropyl methacrylate and 1-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-3-hydroxypropan-2-yl methacrylate.
EC Number:
700-334-3
Molecular formula:
C17H38O6Si3
IUPAC Name:
Reaction mass of 3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-2-hydroxypropyl methacrylate and 1-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]-3-hydroxypropan-2-yl methacrylate.
Test material form:
other: liquid
Details on test material:
Name: Silyl methacrylate (SiMAA2)
Appearance: Liquid
Purity: 97.0% or higher
Storage condition: Refrigerated (at 10°C or lower).
Storage site: Stored in a test articel storage cabinet (4°C).

Test animals

Species:
rat
Strain:
other: Slc:SD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animals bred at Japan SLC, Inc
- Age at study initiation: 4 weeks old
- Weight at study initiation: Mean body weight of 124.65-126.12g for males and 109.54-110.90g for females
- Fasting period before study: 16 hours of fasting
- Housing: Animal room 2207 in the animal building II, in the barrier-sustained facility. Animals were housed in Stainless steel, wire mesh cages (W37cm x D47cm x H19cm) equipped with urinary trays and a wire mesh bottom were used throughout the acclimatisation and study periods. Five animals were housed in a cage
- Diet: Radiation-sterilized pellet diet Labo stock (Nosan Corporation) was fed ad libitum
- Water: Chlorinated well water supplied using water bottles ad libitum
- Acclimation period: 7 days, 5 animals per cage.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-27 deg C
- Humidity (%): 30-70
- Air changes (per hr): Ca 16 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours per day (7:00 am - 7:00 pm)
- Urinary trays were exchanged twice a week, with new trays containing autoclaved bedding

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: No verchile was used. the substance is a liquid, hence was used as a dosing soultion


DOSAGE PREPARATION (if unusual): 2000 mg/kg of neat substance


Doses:
2000 mg/kg
No. of animals per sex per dose:
2000 mg/kg dose: 5 males/5 females
Control (group given water for injection only): 5 males/5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for general condition continuously until 6 hours after administration and once every day thereafter until Day 14. Body weight was measured just prior to administration and on Days 7 and 14 after administration. Day 0 was defined as the day of administration.
- Necropsy of survivors performed: yes - After 14 days of administration, animals were euthanized by exsanguination under ether anesthesia, and organs and tissues were observed grossly for any abnormalities.
Statistics:
Group means and standard deviations of body weight were calculated for each group. At statistical analysis, the homogeneity of variance was evaluated using F-test, and then student's t-test was applied when the variance was homogeneous; when the variance was heterogeneous, Aspin-Wlch t-test was used. Statistical significance of the difference between control and treated groups was analyzed at the significance level of 5%, and the results were shown as either P<0.05 (lower than 5%) or P<0.01 (lower than 1%).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died in any group of either sex.
Clinical signs:
There were no abnormalities in general condition.
Body weight:
The body weight changes of males and females in the SiMAA2 treated group were comparable to those in the control group and there were no statistically significant differences compared to the controls on any days of measurement.
Gross pathology:
No abnormalities were detected in any group at anatomy conducted at termination of the study.

Any other information on results incl. tables

Results of motality and LD50. Administration of test material via oral route:

Sex  Dose (mg/kg)  Mortality  LD50 (mg/kg) 
Male  Contol  0/5   
Male  2000  0/5  >2000 
 Female  Control  0/5  
 Female  2000  0/5  >2000

Mortality: Number of dead rats/number of treated rats

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, no animals died after single administration of SiMAA2 at 2000 mg/kg and no other toxicological effects were detected.
Executive summary:

According to the OECD guidelines for acute toxicity studies, no further dose levels are necessary when there are no toxic signs at 2000 mg/kg after single oral administration.

Therefore, SiMAA2 was administered once orally to male and female rats at 2000 mg/kg and its toxicity was evaluated.

No animals died in each group of males and females, and LD50 was higher than 2000 mg/kg.

In addition, no treatment-related effects were observed in general conditions, body weight, and anatomy findings.

Under the conditions of the present study, no animals died after single administration of SiMAA2 at 2000 mg/kg, and no other toxicological effects were detected.