Paul H. Siitonen

Lack of Significant Dermal Penetration of Titanium Dioxide from Sunscreen Formulations Containing Nano- and Submicron-Size TiO2 Particles

Titanium dioxide (TiO(2)) is included in some sunscreen formulations to physically block ultraviolet radiation. A dermal penetration study was conducted in minipigs with three TiO(2) particles (uncoated submicron sized, uncoated nano-sized, and dimethicone/methicone copolymer-coated nanosized) applied 5% by weight in a sunscreen. These and control formulations were topically applied to minipigs at 2 mg cream/cm(2) skin (4 applications/day, 5 days/week, 4 weeks). Skin (multiple sites), lymph nodes, liver, spleen, and kidneys were removed, and the TiO(2) content was determined (as titanium) using inductively coupled plasma mass spectroscopy. Titanium levels in lymph nodes and liver from treated animals were not increased over the values in control animals. The epidermis from minipigs treated with sunscreens containing TiO(2) showed elevated titanium. Increased titanium was detected in abdominal and neck dermis of minipigs treated with uncoated and coated nanoscale TiO(2). Using electron microscopy-energy dispersive x-ray analysis, all three types of TiO(2) particles were found in the stratum corneum and upper follicular lumens in all treated skin samples (more particles visible with coated nanoscale TiO(2)). Isolated titanium particles were also present at various locations in the dermis of animals treated with all three types of TiO(2)-containing sunscreens; however, there was no pattern of distribution or pathology suggesting the particles could be the result of contamination. At most, the few isolated particles represent a tiny fraction of the total amount of applied TiO(2). These findings indicate that there is no significant penetration of TiO(2) nanoparticles through the intact normal epidermis.

Quantitative Determination of Skin Penetration of PEG-Coated CdSe Quantum Dots in Dermabraded but not Intact SKH-1 Hairless Mouse Skin

Many cosmetics, sunscreens, and other consumer products are reported to contain nanoscale materials. The possible transdermal absorption of nanoscale materials and the long-term consequences of the absorption have not been determined. We used polyethylene glycol coated cadmium selenide (CdSe) core quantum dots (QD; 37 nm diameter) to evaluate the penetration of nanoscale material into intact, tape stripped, acetone treated, or dermabraded mouse skin. QD were suspended in an oil-in-water emulsion (approximately 9 microM) and the emulsion was applied at 2 mg/cm(2) to mouse dorsal skin pretreated as follows: intact; tape stripped to remove the stratum corneum; acetone pretreated; dermabraded to remove stratum corneum and epidermis. QD penetration into the skin was monitored in sentinel organs (liver and regional draining lymph nodes) using inductively coupled plasma mass spectrometry analysis of cadmium (from the CdSe QD). No consistent cadmium elevation was detected in the sentinel organs of mice with intact, acetone pretreated, or tape-stripped skin at 24- and 48-h post-QD application; however, in dermabraded mice, cadmium elevations were detected in the lymph nodes and liver. QD accumulation (as cadmium) in the liver was approximately 2.0% of the applied dose. The passing of QD through the dermabraded skin was confirmed using confocal fluorescence microscopy. These results suggest that transdermal absorption of nanoscale materials depends on skin barrier quality, and that the lack of an epidermis provided access to QD penetration. Future dermal risk assessments of nanoscale materials should consider key barrier aspects of skin and its overall physiologic integrity.

Minimal Behavioral Effects from Moderate Postnatal Lead Treatment in Rats

Developmental lead exposure continues to be a worldwide problem. This study investigated the behavioral effects resulting from developmental lead treatment in rats with corresponding physiological measures of lead exposure. Sprague-Dawley rats were treated with 350 ppm lead acetate from birth to weaning via the dams drinking water. Behavioral measures assessed in the offspring included residential activity tests, complex maze performance, acoustic startle response, emergence behavior (light/dark preference), prepulse inhibition, and ethological assessments of play, dominance, and burrowing. Pb blood levels averaged 53 microg/dl in the dam at the time of offspring weaning and 46 microg/dl in weanling female offspring. Pb levels averaged 277 ng/g and 32 microg/g in the brain and bone, respectively, of female offspring at weaning. No behavioral assessment indicated any lead-related functional alterations nor were there any statistically significant differences when the lead-treated group was restricted to rats in those litters that were above the median Pb blood lead level at weaning. These results indicate that any lead-related functional alterations at this dose may be subtle and require a sufficient demand on the system for detection.

Impact of membrane desolvation on the effects of sodium on response in inductively coupled plasma atomic emission spectrometry with ultrasonic sample introduction

This report compares the influence of sodium on response with ICP-AES for copper, cadmium, lead and cobalt with ultrasonic sample introduction in the presence and absence of a microporous membrane desolvation (MMD). Comparisons are reported at viewing positions of 8, 14, and 20 mm above the load coil, for injector gas flow rates of 0.70, 0.85 and 1.00 l min–1, and at sodium concentrations ranging from 0.00 to 0.08 M Na. Blank emission intensities were depressed in the presence of sodium regardless of the operating condition(s). Depressions in the blank emission intensities were greater without the MMD, but were less than 20%. The magnitude of depression in the blank emission intensities did not vary significantly among the analyte lines or with the viewing position. The impact of sodium on signal intensities with and without the MMD was greater than the impact on the blank emission intensities, with changes approaching 150%. At the lower viewing positions, signal enhancement in the presence of sodium was common and the degree of enhancement was greater with the MMD. Response changes with respect to sodium concentration were also different with and without the MMD low in the plasma. Higher in the plasma, element-to-element variation occurred in the nature of the impact of sodium. For signals that were enhanced, the degree of enhancement was generally greater with the MMD, but when signals were depressed, there was no correlation to the presence or absence of the MMD. In contrast to the lower viewing position, higher in the plasma response changes with respect to the sodium concentration were similar. These results suggest that although the plasma is physically different with and without the MMD, the MMD does not alter the mechanism(s) by which sodium impacts response.

Communication. Aerosol-phase assisted sample digestion for the determination of trace metals in organic samples by plasma atomic emission spectrometry

This report provides evidence of on-line, aerosol-phase assisted sample digestion with ICP-AES detection. In brief, sucrose samples were subjected to a preliminary digestion and were then analysed with and without a membrane separator/desolvator. In the presence of the desolvator, spike recoveries, for various metals including As, Cd, Cu, Pb and Sn, were higher and demonstrated better precision compared with results obtained for digests analysed without the membrane desolvator. This suggests that additional decomposition was occurring in the aerosol phase and that the decomposition products (gaseous NO2 and CO2) were removed from the aerosol flow stream by the membrane desolvator. For sucrose samples spiked at 100 ng g–1 with Pb and digested by an open-vessel procedure, the average recovery (n= 5) improved from 25 to 106% when the digests were analysed with the desolvator. The RSD improved from 76 to 7.3% by the addition of the desolvator. Improved performance without the desolvator could only be achieved by the addition and evaporation of an excess of oxidizing agents which increases cost, analysis time and the chance for environmental contamination. With closed-vessel digestion, sucrose samples spiked with lead at 1.0 µg g–1 demonstrated improvement in the average recovery from 19 to 84% when analysed with the desolvator. Similarly, the RSD decreased from 21 to 4.6% by the addition of the desolvator. In addition to Pb, similar improvements were demonstrated for As, Cd, Cu and Sn by the closed vessel procedure.