Reaction mass of 3-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethylpentasiloxanyl)propoxy]-2-hydroxypropyl 2methylprop-2-enoate and 1-[3-(9-butyl-1,1,3,3,5,5,7,7,9,9-decamethylpentasiloxanyl)propoxy]-3-hydroxypropan-2-yl 2-methylprop-2-enoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 September 2006 to 31 October 2006

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:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2R)-1-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-2-yl 2-methylprop-2-enoate; (2R)-2-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-1-yl 2-methylprop-2-enoate; (2S)-1-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-2-yl 2-methylprop-2-enoate; (2S)-2-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-1-yl 2-methylprop-2-enoate

EC Number:

700-043-1

Molecular formula:

C24H56O8Si5

IUPAC Name:

(2R)-1-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-2-yl 2-methylprop-2-enoate; (2R)-2-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-1-yl 2-methylprop-2-enoate; (2S)-1-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-2-yl 2-methylprop-2-enoate; (2S)-2-hydroxy-8,8,10,10,12,12,14,14,16,16-decamethyl-4,9,11,13,15-pentaoxa-8,10,12,14,16-pentasilaicosan-1-yl 2-methylprop-2-enoate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Compound A
-Lot numbeer: T060620
- Appearance: clear to mild yellowish transparent liquid

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River laboratories Japan, Inc
- Age at study initiation: 7 weeks
- Weight at study initiation: 160-190 g
- Fasting period before study: From the afternoon of the day before the administration unitl the observation at 4 hours after the administration.
- Housing: Metal rat cage 380 x 240 x 170 (mm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Allowable range 19-25°C. Actual temperature measured during the quarantine and acclimation period: 22.7-23.3°C.
Actual temperature measured during the administration and observation period: 22.0-23.1°C
- Humidity (%): Allowable range 40-60
Actual humidity measured during the administration and observation period: 51.0–57.9%RH
- Air changes (per hr): Over 10 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

Dosing solution was prepared on the day of administration and used immediately afterpreparation.
(1) Test article: Compound A
(2) Administration solvent
Name: Japanese Pharmacopoeia Sesame oil
Specification: Japanese Pharmacopoeia
Manufacturer: Yoshida Pharmaceutical Co., Ltd.
Lot number: 659
(3) Preparation method: Compound A was measured for the amount needed, and then dosing solution was prepared for the predetermined concentration by adding the sesame oil.

Administration
Administration was preformed the day after the grouping.
(1) Age of animals at administration
Study 1: 8 weeks of age
Study 2: 9 weeks of age
Study 3: 10 weeks of age
Study 4: 10 weeks of age
(2) Administration route and the reasons for choice
Oral administration.
The reasons for selection of the administration route: followed OECD revised 423.
(3) Administration method and the reasons for selection
The administration dose was 5 mL/kg. The predetermined amount of dosing solution was given orally via gavage using syringes with oral feeding needles for rats. The reasons for selection for administration method: it is a standard method for oral administration.
(4) Administration period, frequency, and time slot and the reasons for selection
Administration was once on Day 1 and performed in the morning (9:24–9:53).
The reasons for selection: followed OECD revised 423.
(5) Fasting
Animals were fasted from the afternoon (16:20–16:30) of the day before administration until the observation at 4 hours after the administration. After the observation, feeding (ad libitum) was resumed

Doses:

300 mg/kg
2000 mg/kg

No. of animals per sex per dose:

6 at 300 mg/kg
6 at 2000 mg/kg

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The observation period was for 14 days, from Day 1 (administration day) to Day 14, and viability and general condition were observed immediately at the administration (administration–15 minutes after), 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours after the administration. On the days except for the administration day, animals were observed for viability and secondarily general condition in the morning (8:30–12:00) while only viability was observed in the afternoon (15:00–17:00). However, observation of viability and general condition was conducted only once in the morning (8:30–12:00) on holidays.

Bodyweight: Animals were weighed in the morning of Day 1, 2, 3, 4, 5, 6, 7, 10, and 14.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology.

Statistics:

Statistical method used for data processing and analysis was not performed.

Results and discussion

Preliminary study:

In order to evaluate acute toxicity, 300 mg/kg was administered once orally as initial dose (study 1) to 3 female rats. Since no death was confirmed in the study further studies were performed in incremental steps.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No statistical method for 95% CL provided.

Mortality:

There was no death in any study and dose level.
Study 1: 300 mg/kg
Study 2: 300 mg/kg
Study 3: 2000 mg/kg
Study 4: 2000 mg/kg

Clinical signs:

other: No specific abnormality was seen in general condition.

Gross pathology:

No specific abnormalities were seen in the anatomic pathology examinations.

Other findings:

- Potential target organs: N/A
- Other observations: In study 1 where 300 mg/kg was administered, loose stool was observed in 2 out of 3 cases at only 2 hours after adminstration.
- Organ weights: There were no gross changes observed.
- Histopathology: No abnormalities

Any other information on results incl. tables

No death was confirmed in any of the studies with 300 mg/kg and 2000 mg/kg administration, and no specific abnormality was seen in general condition, weight changes, or anatomic pathology examination. Based on the above results, LD50 of Compound A in female rats was 2000 mg/kg and above and it was considered not applicable as poisonous and deleterious substance.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

LD50 in female rats was 2000 mg/kg and above and it was considered not acutely by oral ingestion.

Executive summary:

In an acute oral toxicity study (OECD 423), groups of female Crl:CD(SD) rats were given a single oral dose of Mono(hydroxymethacryloxypropoxypropyl) Polydimethylsiloxane in sesame oil at doses of  300 or 2000 mg/kg bw.  Animals were then observed for 14 days.

 

Oral LD₅₀

Females =  greater than 2000 mg/kg bw

 

The substance is of Low Toxicity based on the LD₅₀ in female rats.

No death was confirmed in any of the studies with 300 mg/kg and 2000 mg/kg administration, and no specific abnormality was seen in general condition, weight changes, or anatomic pathology examination.

 

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 423) in the rat.