Scientists from academia, industry, and government reviewed current international regulations for the screening of commercial chemicals for bioaccumulation in the context of the current state of bioaccumulation science. On the basis of this review, several recommendations were proposed, including a scientific definition for "bioaccumulative substances," improved criteria for the characterization of bioaccumulative substances (including the trophic magnification factor and the biomagnification factor), novel methods for measuring and calculating bioaccumulation properties, and a framework for screening commercial chemicals for bioaccumulative substances. The proposed framework for bioaccumulation screening improves current practices by reducing miscategorization, making more effective use of available bioaccumulation data that currently cannot be considered, reducing the need for animal testing, providing simpler and cheaper test protocols for animal studies in case animal studies are necessary, making use of alternative testing strategies, including in vitro and in silico metabolic transformation assays, and providing a scientific foundation for bioaccumulation screening that can act to harmonize bioaccumulation screening among various jurisdictions.

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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...

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The purpose of these experiments was to determine the potential estrogenic, androgenic, and progestagenic activity of two cyclic siloxanes, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5). Receptor-binding experiments and a luciferase reporter gene assay were used to determine if the materials were able to bind and activate either the estrogen receptors (ERs) or progesterone receptors (PRs)-alpha or beta. The rat uterotrophic assay (RUA) for estrogenic activity and the Hershberger assay for androgenic activity were utilized as the in vivo assays. For the ER-binding studies, D4 was shown to bind to ERalpha but not to ERbeta. D5 did not bind to either of the two receptors. D4 activated the reporter gene at 10 microM, while D5 was considered negative in the estrogen reporter gene assay. Neither material was a ligand for the PRs. Both the RUA and Hershberger assays were conducted using whole-body inhalation of the two materials for 16 h/day. D4 resulted in a small but significant increase in both wet and blotted uterine weight as well as increases in both luminal and glandular epithelial cell height in both Sprague Dawley and Fischer 344 rats. D5 was negative in both rat strains, indicating that D5 does not possess estrogenic activity. Neither material possessed any significant antiestrogenic activity. Both materials were negative in the Hershberger assay indicating that neither material possesses any significant androgenic activity. Our studies have shown that D4 exhibits a low affinity for ERalpha in vitro and a weakly estrogenic response in vivo.

In this study, data for human dermal absorption of octamethylcyclotetrasiloxane, D(4), and decamethylcyclopentasiloxane, D(5), through axilla skin in vivo are interpreted using pharmacokinetic models of dermal absorption by adding the dermal exposure route to inhalation physiologically based pharmacokinetics models developed previously. The compartmental model describing dermal absorption of these compounds included volatilization of the applied chemical from the skin surface, diffusion of absorbed chemical back to the skin surface and evaporation of this chemical from the skin surface after the applied dose had cleared from the application site, uptake from the skin compartment into blood, and a storage compartment within the skin. Data from exposures in volunteers (i.e., D(4) and D(5) concentrations in exhaled air and plasma) were used to estimate model parameters. In volunteers exposed to either D(4) or D(5), the maximum concentration of chemical in exhaled air reached a maximum at or prior to 1 h following administration of the test chemical. Based on model calculations, the percent of applied dose of D(4) that was absorbed into systemic circulation for men and women was 0.12 and 0.30%, respectively; for D(5) about 0.05% of the applied dose was absorbed for both men and women. For both D(4) and D(5), model calculations indicate that more than 83% of the chemical that reached systemic circulation was eliminated by exhalation within 24 h. These whole-body pharmacokinetic models for dermal absorption of two semi-volatile compounds provide a valuable tool for understanding factors controlling their dermal absorption through axilla skin and for applying results from these studies in consumer product risk assessments.

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