Modeling of Human Dermal Absorption of Octamethylcyclotetrasiloxane (D4) and Decamethylcyclopentasiloxane (D5)

Abstract

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.

Evaporation of decamethylcyclopentasiloxane (D5) from selected cosmetic products: Implications for consumer exposure modeling

“…For a comparison with earlier evaporation studies (Koini et al, 1999;Reddy et al, 2007) evaporation rates of pure D5 were measured gravimetrically under similar experimental conditions (see Table 1). Hence, 80 μL and 350 μL of neat substance were applied with a micropipette on Petri dishes (diameter = 7.5 cm) covered with filter paper (Schleicher & Schuell AG, Switzerland) of the same diameter and placed on analytical scales (Mettler Toledo, Germany; model AT460 Delta Range, σ = 0.1 mg/1 mg) in a draft free environment.…”

“…2a) evaporation and dermal absorption of neat D5 are both described as zeroorder processes with rates k evap and k 1 [mg cm −2 min −1 ], respectively, where k evap was fixed to the value determined in the chamber experiments with aluminum foil. Absorption into the skin is described as a zero-order process (Reddy et al, 2007) because the driving force for mass transfer (i.e. the concentration gradient) from a film of pure substance on the skin is maximal when the concentration of the substance in the skin is far from saturation.…”

“…Acknowledging the fact that consumer products designed for topical applications are usually complex and often non-aqueous systems containing multiple ingredients, researchers attempted to investigate the influence of the formulation on dermal absorption (Reifenrath and Robinson, 1982;Saiyasombati and Kasting, 2003) and evaporation (Nihi et al, 2009;Vuilleumier et al, 1995) for a range of VOCs. Several studies were also conducted for decamethylcyclopentasiloxane (D5) (Jovanovic et al, 2008;Koini et al, 1999;Reddy et al, 2007;Wang et al, 2011), a highly lipophilic (logK ow = 8.0) and volatile (P = 33 Pa at 25°C) compound that is incorporated into a variety of C&PCPs as a carrier solvent and emollient (Dudzina et al, 2014;Horii and Kannan, 2008;Wang et al, 2009). However, despite the fact that the respective experiments were all designed to mimic realistic application of C&PCPs, their results vary largely, indicating the need of more consistent research.…”

A survey of cyclic and linear siloxanes in indoor dust and their implications for human exposures in twelve countries

“…The siloxane exposure doses calculated from dust ingestion were 3 to 5 orders of magnitude lower than the exposure doses from dermal intake through the use of personal care products. Furthermore, it has been shown that 0.12-0.3% and 0.05% of the dermally applied dose of D4 and D5, respectively, were absorbed into the systemic circulation (Reddy et al, 2007). A no-observed adverse effect level (NOAEL) of 19 mg/kg/d was reported for D5 based on a 90-day inhalation exposure study in rats (Brooke et al, 2009a,b,c), and the exposure doses estimated from indoor dust ingestion were several orders of magnitude lower than the NOAEL.…”

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

“…The absorption is around 52 per cent of the dose in corn oil, around 12 per cent of the dose in simethicone, and 28 per cent of the dose as a neat substance. Anderson (2005) and Reddy et al (2004Reddy et al ( , 2005) also carried out physiologically based pharmacokinetic modelling for both inhalation and dermal exposure to D5 and D4 (CES, 2005a). These models are based on a comprehensive data set that included both single and repeated inhalation studies in rats, a single-inhalation exposure study in humans, and both in vitro and in vivo percutaneous absorption studies.…”