Metabolites of Hexamethyldisiloxane and Decamethylcyclopentasiloxane in Fischer 344 Rat Urine—A Comparison of a Linear and a Cyclic Siloxane

Abstract

were obtained using a high-pressure liquid chromatography (HPLC) system equipped with a radioisotope detector. The metabolite elution was carried out on a C 18 column using an acetonitrile/ water mobile phase. The structural assignments were based on GC-MS analysis of the tetrahydrofuran extract of urine containing the metabolites. Some of the metabolites in the extracts were first protected with trimethylsilyl groups prior to GC-MS analysis using bis(trimethylsiloxy)trifluoroacetamide or highly purified hexamethyldisiloxane. Hexamethyldisiloxane (MM, HMDS 1 ), the smallest member of the polydimethylsiloxane polymers, and decamethylcyclopentasiloxane (D 5 ), a cyclic siloxane are colorless volatile fluids. MM is quite volatile with a vapor pressure of 42.2 mm Hg at 25°C and a boiling point of 100°C (Flanningam, 1986). D 5 is relatively less volatile with a vapor pressure of 2 mm Hg at 50°C and a boiling point of 210°C. The aqueous solubilities of MM and D 5 are 930 and 17 ppb, respectively (Varaprath et al., 1996). The primary use of MM and D 5 is as intermediates in the manufacturing of high molecular weight siloxane polymers. MM and D 5 also find use as vehicles or ingredients in a wide range of consumer product formulations (Cameron et al., 1986) since they have several favorable properties such as low surface tension, adequate evaporation rate, lack of odor, high degree of compatibility with many consumer product ingredients, and low toxicity. Typical examples of applications include moisturizing creams, lotions, bath oils, colognes, shaving products, and perfumes. Besides these product applications, they are also used as cleaners, lubricants, and penetrating oils.The rigorously purified MM (Dow Corning OS-10, purity Ͼ99.9%) is one of the many ozone-safe volatile methylsiloxanes that is exempt from federal volatile organic compound regulations and hence is accepted as an alternative for other organic solvents. Another important industrial use of MM is as a chain-terminating agent in siloxane polymerizations. The use of MM and D 5 in various product formulations necessitated conducting chemical and environmental fate/effects tests of them.Potential human exposure to MM and D 5 can result at the work place during the manufacturing process, as well as through the normal use of consumer products that contain them. Only sparse toxicological information is available on these siloxanes since they are believed to be relatively inert and of low toxicity. However, octamethylcyclotetrasiloxane (D 4 ), a homolog of D 5 had been extensively studied. In rodents, inhalation exposure to D 4 results in dose-related hepatomegaly, transient hepatic hyperplasia, hypertrophy, and induction of hepatic cytochrome P450 enzymes in a fashion similar to phenobarbital (McKim et al., 1998(McKim et al., , 2001). Very limited toxicity data are available on HMDS and D 5 in biological systems. In a 13-week subchronic MM whole-body inhalation, renal histopathology consis-1 Abbreviations used are: MM, (HMDS) hexamethyldisiloxane; D 5 , decame...

Methyl Siloxanes in Environmental Matrices around a Siloxane Production Facility, and Their Distribution and Elimination in Plasma of Exposed Population

“…Due to the lack of reports on hepatic metabolism rates of linear methyl siloxane analogues, our speculation about their metabolism rates trend could not be proved. However, the trends were consisted with results for the cyclic methyl siloxanes in a previous report, 37 which showed that the metabolism rate of D4 was faster than that of D5.…”

Methyl siloxanes in environmental matrices and human plasma/fat from both general industries and residential areas in China

“…Due to their lower volatility, elimination rates of linear siloxanes via exhalation in fat would be lower than those of cyclic compounds. In addition, it was reported that hexamethyldisiloxane (L2) could be metabolized via oxidation in liver (Varaprath et al, 2003). L8-L10, as the homologues of L2, could undergo the similar metabolism.…”

Temperature Dependence of the Organic Carbon/Water Partition Ratios (KOC) of Volatile Methylsiloxanes

“…CES (2005a) summarises the available mammalian uptake and metabolism data for D4 [including a number of unpublished studies and taking into account published work by Varaprath et al (1999Varaprath et al ( , 2003, , Andersen et al (2001), and Sarangapani et al (2003) on both D4 and D5]. Most of the available mammalian toxicokinetic and toxicity data were obtained using inhalation exposure (as this is one of the primary routes of exposure of humans and, given the volatility of D4, it is significantly easier to test the substance by this route of exposure than by dermal and oral routes), but dermal and oral exposure have also been considered.…”