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: dermal

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

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:

Sponsor's identification: OH-mPDMS
Description : clear colourless liquid
Lot number : 17554.025
Date received : 03 March 2008
Storage conditions: room temperature in the dark

Test animals

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

Administration / exposure

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.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

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.

Applicant's summary and conclusion

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.