Inhalation toxicity of cyclic semi-volatile methylsiloxanes: Disentangling the conundrum of phase-specific adaptations from adverse outcomes
A new study on inhalation toxicity of cyclic semi-volatile methylsiloxanes: Disentangling the conundrum of phase-specific adaptations from adverse outcomes.
Highlights of the study:
• The inhalation toxicity of (semi-)volatile cyclic methylsiloxanes (cVMSs) increases at supersaturated concentrations.
• Aerosols of cVMSs were shown to impart portal-of-entry effects adaptive in nature and non-cumulative.
• These response did not progress from short-to long-term exposure suggesting adaptation to high inhaled dose.
• Experimental inhalation studies with cVMSs require high specialization to prevent aerosol phase-specific artifacts.
This paper compares the phase-specific inhalation toxicity of the cyclic semi-volatile methylsiloxanes (cVMSs) D4, D5 and D6. The objectives of this paper are to re-analyze information from acute to chronic inhalation studies on rats with these cVMSs to identify the unifying principles of phase-specific toxicity at the portal-of-entry and if they depend on acute, acute-on-chronic or chronic mechanisms. This re-analysis supports the hypothesis that concentrations must be high enough to exceed the vapor saturation at any given temperature for stabilizing the aerosol phase and evoking phase-specific effects at sites of the respiratory tract susceptible to the cVMSs-specific physicochemical properties amphiphilicity and surface tension. In summary, the portal-of-entry effects and related findings appear to be acute in nature and specific to liquid aerosol. The repeated inhalation exposure studies with D4 and D5 up to two years in duration did not reveal chronic aggravations of portal of entry outcomes. Findings at a pulmonary location where amphiphilic surfactant molecules are present appear to be caused by the acute adaptation to deposited dose. Such outcome should better be described as a high-dose liquid aerosol phenomenon imparted by the physicochemical properties “liquid” and “hydrophobic”. This calls for a phase-specific human risk characterization of cVMSs.
The study can be found under this link.