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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 4 2002 to October 25, 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 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

10-hydroxy-2,2,4-trimethyl-4-[(trimethylsilyl)oxy]-3,8-dioxa-2,4-disilaundecan-11-yl 2-methylprop-2-enoate; 11-hydroxy-2,2,4-trimethyl-4-[(trimethylsilyl)oxy]-3,8-dioxa-2,4-disilaundecan-10-yl 2-methylprop-2-enoate

EC Number:

700-334-3

Molecular formula:

C17H38O6Si3

IUPAC Name:

10-hydroxy-2,2,4-trimethyl-4-[(trimethylsilyl)oxy]-3,8-dioxa-2,4-disilaundecan-11-yl 2-methylprop-2-enoate; 11-hydroxy-2,2,4-trimethyl-4-[(trimethylsilyl)oxy]-3,8-dioxa-2,4-disilaundecan-10-yl 2-methylprop-2-enoate

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: Rats bred at Japan SPLC, Inc.
- Age at study initiation: 6 weeks old.
- Weight at study initiation: Males: Mean weight of test group = 232.85 g. Females: Mean weight of test group = 166.28 g
- Fasting period before study: None.
- Housing: Stainless steel wire mesh cages (W37 × D47 × H19 cm) equipped with urinary trays and wire mesh bottom were used during the
acclimatization period. Urinary trays were exchanged twice a week with new trays containing autoclaved bedding (Softchip of fir). Aluminum cages (W25 × D40 × H18 cm) were used during the study period. Cages were exchanged twice a week with new ones containing autoclaved fresh and clean bedding. Five animals were housed in a cage during the acclimatization period and one animal after grouping.
- Diet (e.g. ad libitum): Radiation-sterilized pellet diet was fed ad libitum
- Water (e.g. ad libitum): Chlorinated well water was supplied using water bottles ad libitum
- Acclimation period: 7 days prior to study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 27°C
- Humidity (%): 30 - 70%
- Air changes (per hr): approximately 16 times per hour
- Photoperiod (hrs dark / hrs light): illumination for 12 hours/day

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 24 hours prior to administration, fur was clipped from the dorsal area of the trunk with an electric clipper.
- % coverage: The test article was applied evenly over an area approximately 10% of the body surface area.
- Type of wrap if used: The area was covered with a porous gauze dressing throughout the exposure period of 24 hours and the attachment between the test article and the skin was further secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not stated.
- Time after start of exposure: 24 hours.

TEST MATERIAL
Dose concentration: 2000 mg/kg.
The administration volume was calculated individually based on the body weight on the day of administration.

VEHICLE
Not applicable. Since the test article was liquid, it was used as a dosing solution as it was.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg.

No. of animals per sex per dose:

5 males and 5 females at 2000 mg/kg.

Control animals:

other: A group of 5 males and 5 females were given water for injection only as a control.

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-Welch t-test was used. Statistical significance of the difference between the 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:

other: There were no abnormalities in general condition.

Gross pathology:

At necropsy conducted at termination of the study, a hepatodiaphragmatic nodule was observed in one male in the 2000 mg/kg group. The lesion was, however, considered incidental because of its severity as well as the fact that the change is frequently observed in the untreated control group. There were no other abnormalities in any group.

Any other information on results incl. tables

Table 1: Mortality and LD50

 

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

Table 2: Group mean body weight

 

Sex	Dose (mg/kg)	Days after administration
			-1	7	14
Male	Control	N	5	5	5
		Mean	230.98	278.27	315.70
		S.D.	4.55	8.90	11.65
	2000	N	5	5	5
		Mean	232.85	286.64	329.42
		S.D.	5.25	14.26	19.37
Female	Control	N	5	5	5
		Mean	163.17	184.00	198.13
		S.D.	4.59	8.76	7.68
	2000	N	5	5	5
		Mean	166.28	187.70	200.74
		S.D.	7.22	10.24	11.65

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

SiMAA2 was administered once dermally 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 the LD50 was higher than 2000 mg/kg.

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 dermal administration.

 

Therefore, SiMAA2 was administered once dermally 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.