Hexamethylcyclotrisiloxane

Endpoint summary

Description of key information

There are no reliable acute oral toxicity data available for hexamethylcyclotrisiloxane (D3; CAS no. 541-05-9; EC No. 208-765-4

), therefore all the available key acute oral toxicity data for other analogue cyclic siloxanes (octamethylcyclotetrasiloxane (D4; CAS No. 556-67-2; EC No. 209-136-7); decamethylcyclopentasiloxane (D5; CAS No. 541-02-6; EC No. 208-764-9); dodecamethylcyclohexasiloxane (D6; CAS No. 540-97-6; EC No. 208-762-8)) have been read across as a weight of evidence. See attachment to Section 13 for justification of read-across.

 

In the acute oral toxicity study with octamethylcyclotetrasiloxane (D4) in male rats (Bayer AG, 1979), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but prior to GLP compliance, the LD50 was greater than 4800 mg/kg bw.   

In the acute oral toxicity study with decamethylcyclopentasiloxane (D5) (Toxikon Corporation, 1990), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 value for male and female rats was >5000 mg/kg bw.

In the acute oral toxicity study with dodecamethylcyclohexasiloxane (D6) (NOTOX, 1999), conducted according to OECD Test Guideline 423 and in compliance with GLP, the LD50 value was >2000 mg/kg bw.

No acute inhalation tests are available for D3. However, a repeated dose toxicity study via the inhalation route (Dow Corning Corporation, 2001) tested D3 at exposure levels up to the maximum attainable vapour concentration for this substance, for a duration of 6 hours per day for 90 days. There was no mortality or evidence of specific target organ toxicity in this study. It can therefore be concluded that D3 would not be acutely toxic by the inhalation route up to the maximum attainable vapour concentration. 

 

No data are available for the dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

A single oral administration of 5 ml/kg of test substance to 10 male rats. Observation period 14 days.

GLP compliance:

no

Test type:

other: LD50

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Wikelmann

- Weight at study initiation: 160-180g

- Housing: 5 animals per cage

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No detail available.

Doses:

5.0 ml/kg bw

No. of animals per sex per dose:

10M

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: no detail available

- Necropsy of survivors performed: not specified

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: No detail available.

Statistics:

No statistical analysis reported.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 800 mg/kg bw

Based on:

test mat.

Mortality:

No mortality.

Clinical signs:

other: No clinical signs.

Gross pathology:

None reported.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An acute oral LD50 value of > 5 ml/kg (equivalent to 4800 mg/kg bw) was determined in male rats in a reliable study conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but prior to GLP compliance.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The test was conducted based upon the Federal Hazardous Substances Act - Consumer Product Safety Commission, 16 CFR, Part 1500, Chapter 2, Subpart C, Section 1500.3, 1990.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River Breeding laboratories (Wilmington, MA)

- Age at study initiation: 8-12 weeks old

- Weight at study initiation: 200-300 g bw

- Fasting period before study: overnight

- Housing: individually housed using stainless steel cages

- Diet: commercial rodent ration, ad libitum

- Water: municipal tap water, ad libitum

- Acclimation period: 3 day quarantine upon receipt



ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 +/-3

- Humidity (%): 30-70

- Air changes (per hr): min. 10-13

- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data available.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Clinical observations were conducted daily and included all toxicologic and pharmacologic signs including nature, onset, severity and duration of abnormal or unusual cardiovascular, respiratory, excretory, behavioural and other activities, as well as signs including adverse effect on the central nervous system (paralysis, lethargy, lack of coordination and staggering) and time of death. Individual body weights were determined on the fasted animals on day 0 (shortly before the test article was administered) and again on study day 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: A gross necropsy was performed on all animals on day 14.

Statistics:

No statistical analysis performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: There were no overt signs of toxicity noted in any test animal during the observation period.

Gross pathology:

No unusual lesions were noted in any of the animals at necropsy.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An acute oral LD50 value of >5000 mg/kg for male and female rats was determined in a reliable study conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1999/05/11-1999/05/26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River Deutschland, Germany

- Age at study initiation: ca. 6 weeks old

- Weight at study initiation: 147g females, 194g males

- Fasting period before study: over night

- Housing: Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material

- Diet: standard pelleted laboratory animal diet, ad libitum

- Water: tap water, ad libitum

- Acclimation period: min. 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 21

- Humidity (%): 50

- Air changes (per hr): ca.15

- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.22 ml/kg bw

Doses:

2000 mg/kg

No. of animals per sex per dose:

3M, 3F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Mortality and viability was checked twice, daily. Body weights were recorded on day 1 (pre-administration), day 8 and day 15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:Clinical signs were checked at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded. Macroscopic examination was performed after terminal sacrifice.

Statistics:

No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs of toxicity were noted. 

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

In the acute oral toxicity study, conducted according to the toxic class method OECD Test Guideline 423 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg bw was concluded.

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

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no reliable acute oral toxicity data available for hexamethylcyclotrisiloxane (D3), therefore all the available acute oral toxicity data for cyclic (octamethylcyclotetrasiloxane; decamethylcyclopentasiloxane; dodecamethylcyclohexasiloxane) analogue siloxanes have been read-across as a weight of evidence.

In the acute oral toxicity study with hexamethylcyclotrisiloxane (D3), which appeared to have been conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but with very limited documentation for assessment and not in compliance with GLP, 2 male and 2 female rats were given a single oral gavage dose of 5.2, 7.7, 10.4 and 15.4 g/kg. The animals were then observed for clinical signs of toxicity for 14 days. All animals were weighed and observed at intervals during the observation period or until any weight loss was regained and the animals appeared healthy. Pathological observation was made on representative animals when indicated. There is not information about necropsy evaluation. There were no mortalities throughout the study period. The study reports an ALD50 value of >15.4 g/kg. This study adds to the weight of evidence that D3 is not acutely toxic via the oral route; this conclusion is supported by the data for cyclic analogues which are read across.

In the acute oral toxicity study with octamethylcyclotetrasiloxane (D4) in male rats (Bayer AG, 1979), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but prior to GLP compliance, 10 male Wistar rats were administered a single oral gavage dose of 5.0 ml/kg bw D4 (4800 mg/kg bw). The animals were then observed for 14 days for mortality and signs of toxicity. At the end of the observation period the animals were sacrificed and a histopathological examination conducted and organ weights recorded (organs not specified). There were no adverse findings reported. There were no deaths or clinical signs of toxicity at this dose. The LD50 was greater than 4800 mg/kg bw.

In the key acute oral toxicity study with decamethylcyclopentasiloxane (D5) (Toxikon Corporation, 1990a), conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, 5 male and 5 female Sprague-Dawley rats were given an oral gavage dose of 5000 mg/kg bw D5. The animals were then observed for mortality and clinical signs of toxicity for 14 days. A necropsy examination was conducted on each animal following the 14 day observation period. There were no deaths, no signs of toxicity, and growth and necropsy findings were normal. The LD50 for male and female animals was therefore >5000 mg/kg bw.

In the acute oral toxicity study (NOTOX, 1999), conducted according to OECD Test Guideline 423 and in compliance with GLP, a limit dose of 2000 mg/kg bw of the neat dodecamethylcyclohexasiloxane (D6) was administered orally (gavage) to male and female rats. During 14-day observation no treatment-related effects were reported and the LD50 was concluded to be >2000 mg/kg bw.

No acute inhalation studies are available for D3. However, a repeated dose toxicity study via the inhalation route (Dow Corning Corporation, 2001) tested D3 at exposure levels up to the maximum attainable vapour concentration for this substance, for 6 hours per day for 90 days. There was no mortality or evidence of specific target organ toxicity in this study. It can therefore be concluded that D3 would not be acutely toxic by the inhalation route up to the maximum attainable vapour concentration. In accordance with Section 1.1.2 of REACH Annex XI, further testing for acute inhalation toxicity is not required.

Justification for classification or non-classification

Based on the available data for the oral and inhalation routes, D3 does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.