3,3,6,6-tetramethoxy-2,7-dioxa-3,6-disilaoctane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.007 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

37.5

Dose descriptor:

LOAEC

Value:

0.562 mg/m³

AF for dose response relationship:

3

Justification:

Default for LOAEC as point of departure (ECHA IR CSA R.8)

AF for differences in duration of exposure:

1

Justification:

The available acute and repeated dose inhalation studies indicate that the main toxic effect is local damage to the upper respiratory tract. The effect is considered concentration- rather than dose-dependent and expected to equally occur upon both acute and long-term exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Default if route-to-route extrapolation is not needed and doses are expressed as concentrations (ECHA IR CSA R.8)

AF for other interspecies differences:

2.5

Justification:

Default worst case (ECHA IR CSA R.8)

AF for intraspecies differences:

5

Justification:

Default for workers (ECHA IR CSA R.8)

AF for the quality of the whole database:

1

Justification:

Default (ECHA IR CSA R.8)

AF for remaining uncertainties:

1

Justification:

Default (ECHA IR CSA R.8)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.015 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: TRGS 900, BMAS, 2006/2009 and in accordance to ECHA guidance document R.8 (appendix R.8-8, Box 6)

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

A number of inhalation toxicity studies in rats are available for the substance, for both acute and repeated exposure. The substance exhibited severe toxicity, including mortality, even at very low concentrations.

The predominant toxic effect consistently observed in the available studies was local damage to the upper respiratory tract: Severe histopathologic changes were observed in the nasal cavity, pharynx, larynx, trachea and bronchi. No specific systemic effects were observed, and therefore, derivation of systemic DNELs is not meaningful. As the substance has not been identified to be irritating to the skin, no dermal DNELs for local effects are required.

Worker inhalation DNEL - local effects, long term:

The LOAEC of 50 ppb (Siddiqui et al., 1997), corresponding to 0.562 mg/m3 based on local effects to the upper respiratory tract was used as a point of departure. The further derivation steps were conducted in accordance with the ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (v2.1, November 2012):

Correction of starting point: Corrected LOAEC = 0.562 mg/m3 * (6 h/d / 8 h/d) * (6.7 m3 / 10 m3) = 0.28 mg/m3

AF for allometric scaling: 1 (default for local effects)

AF for remaining interspecies differences: 2.5 (default)

AF for intraspecies differences: 5 (default for workers)

AF for exposure duration: 1 (reduced from Guidance default because the main toxic effect is local damage to the upper respiratory tract. The effect is considered concentration- rather than dose-dependent and expected to equally occur upon both acute and long-term exposure.)

AF for dose-response relationship: 3 (default for LOAEC as starting point)

DNEL = 0.28 mg/m3 / 2.5 / 5 / 3 = 0.0075 mg/m3

Worker inhalation DNEL - local effects, short term:

OELs are based on 8-hour time weighted average (TWA) exposures. Short-term peak exposures can be covered by applying a multiplication (ceiling) factor between 1 (default basic value) and 8 (maximum ceiling factor), according to the German rule for OELs (TRGS 900, BMAS, 2006/2009). The primary health effect of the substance via the inhalation route is local damage to the respiratory tract, which are considered to be related to the deposited dose per unit of surface rather than the total dose. Therefore, a DNEL for short-term exposure can be derived from the long-term DNEL of 0.0075 mg/m3 by applying a rather conservative multiplication factor of 2. This proceeding is in accordance with ECHA guidance document R.8 (appendix R.8-8, Box 6).

DNEL = 0.0075 mg/m3 x 2 = 0.015 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

The substance is intended for use in an industrial setting only. As no consumer exposure is anticipated to occur, no DNELs for general population are derived.