Hexamethyldisiloxane

Endpoint summary

Description of key information

In a well conducted in vitro dermal absorption study (Dow Corning Corporation, 2000) conducted to GLP, a statistical analysis of the data indicated that only 0.023% of the applied dose of hexamethyldisiloxane was absorbed through human cadaver skin. The majority of the dose volatilised from the application site (97.5%).

Two toxicokinetics studies are available for HMDS (Dow Corning Corporation, 2006 and 2008), both of which were well conducted. These studies showed that the highest concentrations of HMDS are found in the kidney and fat, the majority of HMDS is eliminated from tissues and blood within 24 hours of exposure and subsequently excreted in urine as polar metabolites, or expired volatiles. 

In a non-GLP study (Dow Corning Corporation, 2001) that investigated the metabolism of HMDS in rats, metabolites (abundant in hydroxymethyl groups) of this linear siloxane were found to be structurally different from that obtained for cyclic siloxanes (D4 and D5, which are mainly silanols) except for the commonly present dimethylsilanediol.

Key value for chemical safety assessment

Absorption rate - dermal (%):

0.023

Additional information

In an in vitro dermal absorption study (Dow Corning Corporation, 2000) using a Bronaugh Flow Through method, human cadaver skin was exposed to the HMDS for 24 hours. A statistical analysis of the data indicated that only 0.023% of the applied dose of HMDS was absorbed through the human cadaver skin. The majority of the dose volatilised from the application site (97.5%).

In a toxicokinetic study (Dow Corning Corporation, 2006) rats were exposed (6-hour nose-only) to HMDS for either

14 consecutive days followed by a single exposure (6-hour) to ¹⁴C-HMDS, or to a single exposure (6-hour) of ¹⁴C-HMDS. All concentrations of HMDS were 5000ppm. In both experiments approximately 4% of the dose was retained. Parent HMDS was measured in blood and tissues; brain, fat, kidney, liver, lung and testes and the highest concentrations were found in fat and kidney. Elimination of radioactivity from blood and tissues (excluding fat) was multiphasic, with the majority of the radioactivity eliminated within 24 hours post-exposure. The majority of systemically absorbed HMDS was eliminated in the urine or expired volatiles. Urinary elimination was as polar metabolites only. Considering the effective removal of HMDS through metabolism and exhalation, the authors of the study considered accumulation in the body after repeated exposures to be unlikely.

After a 6 hour inhalation exposure of female rats to 5000 ppm HMDS, approximately 3% of the achieved dose was retained (Dow Corning Corporation, 2008). Parent HMDS was measured in blood and tissues: brain, fat, kidney, liver, lung and ovaries, and the highest concentrations were found in fat and ovaries. Elimination of radioactivity from blood and tissues (excluding fat) was multi-phasic, with the majority of the radioactivity eliminated within 24 hours post-exposure. The majority of the systemically absorbed HMDS was eliminated in the urine or expired volatiles. Urinary excretion consisted of entirely polar metabolites. The primary route of elimination was in expired volatiles and 71% of this radioactivity was attributed to parent HMDS with the remainder as metabolites. Considering the effective removal of HMDS through metabolism and exhalation, accumulation in the body after repeated exposures is unlikely despite its high lipophilicity.

In a non-GLP study (Dow Corning Corporation, 2001) that investigated the metabolism of HMDS in rats, metabolites (abundant in hydroxymethyl groups) of this linear siloxane were found to be structurally different from that obtained for cyclic siloxanes (D4 and D5, which are mainly silanols) except for the commonly present dimethylsilanediol.