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

Endpoint summary

Description of key information

The acute oral and acute dermal LD50 values of the test substance were >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

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.

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.

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.

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 01 July 2009 and 15 July 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do no effect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wistar (HsdRccHan:WIST) strain rats were supplied by Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: At the start of the study the animals weighed at least 200g.
- Fasting period before study: No.
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): . Free access to food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): . Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature wasset to achieve limits of 19 to 25°C.
- Humidity (%): The relative humidity was set to achieve limits of 30 to 70%.
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From: Day 0 To: Day 14

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks of each animal were clipped free of hair.
- % coverage: The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 hours.


TEST MATERIAL
For the purpose of the study the test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
Dose level (mg/kg): 2000
Specific Gravity: 0.926
Dose volume (ml/kg): 2.16


VEHICLE
Not applicable.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Other examinations performed: After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale. Any other skin reactions, if present were also recorded

Statistics:

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

Preliminary study:

Not applicable.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% CL not appliacalbe.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Dermal Reactions - There were no signs of dermal irritation.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction. 

The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

§        Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

Method. 

A group of ten animals (five males and five females) was given a single, 24‑hour, semi‑occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Dermal Irritation. 

There were no signs of dermal irritation.

Bodyweight. 

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

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute dermal median lethal dose (LD₅₀) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute Oral Toxicity:

In an acute oral toxicity study (OECD 423), groups of female Crl:CD(SD) rats were given a single oral dose of Mono(hydroxymethacryloxypropoxypropyl) Polydimethylsiloxanein sesame oil at doses of  300 or 2000 mg/kg bw.  Animals were then observed for14 days.

 

Oral LD_50:

Females =  greater than 2000 mg/kg bw

 

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 (OECD423) in the rat.

Acute Dermal Toxicity:

Introduction. 

The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§ OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

§ Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

Method. 

A group of ten animals (five males and five females) was given a single, 24‑hour, semi‑occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Dermal Irritation. 

There were no signs of dermal irritation.

Bodyweight. 

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

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute dermal median lethal dose (LD₅₀) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

The substance does not meet the criteria for classification, under the CLP regulations, for acute toxicity via the oral route based on the result of an acute oral toxicity study conducted to OECD Guideline 423, giving an LD₅₀of greater than 2000 mg/kg bodyweight.

The substance does not meet the criteria for classification, under the CLP regulations, for acute toxicity via the dermal route based on the results of an acute dermal toxicity study conducted to OECD Guideline 402, which gave an LD₅₀of greater than 2000 mg/kg bodyweight.