Hydroxytrimethylsilane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

12-06-1989 to 12-02-1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The restrictions were only one dose tested, only 6 animals per sex per group, no haematology or clinical chemistry evaluation, histopathology conducted after 20 years.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

Only one dose tested, only 6 animals per sex per group, no haematology or clinical chemistry evaluation, histopathology conducted after 20 years

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethyldisiloxane

EC Number:

203-492-7

EC Name:

Hexamethyldisiloxane

Cas Number:

107-46-0

Molecular formula:

C6H18OSi2

IUPAC Name:

Hexamethyldisiloxane

Test material form:

other: solution

Details on test material:

- Name of test material (as cited in study report): Hexamethyldisiloxane
- Substance type: siloxane
- Physical state: Liquid
- Stability under test conditions: No data
- Storage condition of test material: No data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily (5 days/week)

Doses / concentrations

Dose / conc.:

1 500 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

SIx

Control animals:

yes

Results and discussion

Effect levels

Key result

Dose descriptor:

LOAEL

Effect level:

1 500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Based on bile duct protoporphyrin accumulation at the the only dose tested

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No treatment-related deaths occurred. There were no clinical signs of toxicity or effects on body weight gains.
Statistically significant increase in the relative kidney weights was observed in male rats. However, no increase in liver weights was noted in either male or female rats.

The addendum reported the following microscopic findings: Dark brown pigment was observed in bile ducts from 4/6 males. Under polarised light the pigment showed red birefringence and 'Maltese cross' patterns and was accompanied by bile duct proliferation and chronic inflammation. In the reported study the brown pigmented material had been observed, but was called bile stasis with an attendant granulomatous cholangitis. It should be noted that bile stasis is a process, not a material and that what would actually have been observed is bile pigment (bile) that was accumulated due to intra- or extra-hepatic obstruction. It does not appear that any stains were used to characterise the material (bile). In the 1990 report the authors hypothesised that the presumptive bile stasis was secondary to dosing errors, i.e. the authors' entire interpretation was erroneous and followed misidentification of the brown pigment. The amendment noted that although the pigment deposits in the old slides often appeared washed out, the classical appearance of protoporphyrin pigment (red birefringence and Maltese cross patterns under polarised light) was observed clearly enough to make a confident diagnosis.

There is ongoing research into the origin of the brown pigment found in bile ducts of some rats treated with some silicon-containing compounds.

Therefore, until this research is completed, the NOAEL/LOAEL is based on the effects on the liver, which were dismissed in 1990.

Applicant's summary and conclusion

Conclusions:

In a 28-day oral gavage study (DCC, 1990), conducted to GLP using a protocol with limitations compared with OECD test guidelines, the NOAEL for hexamethyldisiloxane for effects relevant to humans was less then 1500 mg/kg bw/day, based on bile duct protoporphyrin accumulation at a dose of 1500 mg/kg bw/day (the only dose tested).