EDCs are commonly thought to bind or interfere with estrogen, androgen, progesterone, thyroid, and retinoid receptors. Oxybenzone is considered to be an endocrine-disrupting chemical and approximately 97% of people in the United States were found to have BP3 in their urine. This thesis will address how BP3 affects the innate immune system, in particular myeloid cells. My Master’s thesis aims to address two main overarching questions. Does BP3 alter macrophage polarization, cytokine/chemokine secretion, the viability in vitro? Does exposure to BP3 in vivo during pregnancy/lactation affect the RNA expression of cytokines and immunosuppressant factors associated with the myeloid population? It is unknown how BP3 impacts immune subpopulations in a neoplastic setting. Additionally, it is important to consider how these effects may contribute to malignant behaviors. My thesis evaluates the effects of BP3 on the Raw 264.7 cell lines as well as tumor tissues from mice exposed to BP3 during pregnancy and lactation. We hypothesized that BP3 exposures induce changes in myeloid cell interactions in the immune system through ER-mediated mechanisms. We anticipated that BP3 would increase the growth and migration of 4T1 cells through indirect signals imparted by myeloid cell populations. We also hypothesized that there will be a decrease in T cell proliferation following BP3 exposure and an alteration in gene expression consistent with a shift from Th1 to Th2. Finally, we expected that BP3 exposure would increase the number of myeloid cells in mouse tumors. Our research shows that oxybenzone appears to enhance the pro-inflammatory state of RAW264.7 cells and may result in the release of unidentified factors that can impact 4T1 cell anchorage-independent cell growth in these pro-inflammatory conditions. BP3 may also impact the metabolic activity of recovering RAW264.7 cells following LPS-induced activity. Additionally, BP3 may impact the release of factors from macrophages that control T cell activation-induced proliferation. By using the p53-/- mouse tumors we found that exposure to 3mg/kg/day BP3 during pregnancy and lactation did alter IDO1 RNA expression but this was not associated with markers of immunosuppressive cell types.

Pharmaceuticals and personal care products (PPCPs) are detected routinely in raw and treated municipal wastewater. Conventional wastewater treatment processes are not effective in removing PPCP; therefore, treated wastewater discharges are one of the main entry points for PPCPs into the aquatic environment, and eventually into drinking water supplies. The use of laccase-catalyzed oxidation for removing low concentrations of PPCPs from municipal wastewater after primary treatment is investigated. Oxybenzone was selected as a representative PPCP. Like many other PPCPs, oxybenzone is not recognized directly by the laccase enzyme. Therefore, mediators were used to expand the oxidative range of laccase, and the efficacy of this laccase-mediator system in primary effluent was evaluated. Eight potential mediators were investigated. The greatest oxybenzone removal efficiencies were observed when 2,2’-azino-bis(3-ethylbenzthiazoline-6sulphonic acid) (ABTS), a synthetic mediator, and acetosyringone (ACE), a natural mediator, were present. An environmentally relevant concentration of oxybenzone (10 µg/L) in primary effluent was removed below the detection limit after two hours of treatment with ABTS, and 95% was removed after two hours of treatment with ACE. Several mediator/oxybenzone molar ratios were evaluated at two different initial oxybenzone concentrations. Higher mediator/oxybenzone molar ratios were required at the lower (environmentally relevant) oxybenzone concentrations, and ACE required higher molar ratios than ABTS to achieve comparable oxybenzone removal. The oxidation mechanisms and kinetics of the ACE mediator was evaluated. A better understanding of the mediator oxidation process would lead to a better design of the laccase-mediator system. An alternative laccase-mediator treatment configuration, which allows the enzyme and mediator to react prior to coming in contact with the target PPCP, was investigated. This treatment configuration shows promise for further development since it might reduce laccase and mediator requirements. Oxidation byproducts generated by the laccase-mediator system were characterized and compared to those generated during ozonation. Enzymatic treatment generated byproducts with higher mass to charge (m/z) ratios, likely due to oxidative coupling reactions. The results of this study suggest that, with further development, a laccase-mediator system has the potential to extend the treatment range of laccase to PPCPs not directly recognized by the enzyme, even in a primary effluent matrix. / text

In this thesis, a series of in vitro diffusion studies were performed to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Transdermal permeation of picaridin and oxybenzone from four commercially available repellent and sunscreen products was also investigated by using different application concentrations and sequences. The results obtained were then compared to those of the repellent DEET and the sunscreen oxybenzone under identical experimental conditions. Permeation of picaridin and oxybenzone across human epidermis was suppressed when both compounds were used concurrently. Increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and artificial PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed between the two substances. Transdermal permeation of picaridin across human epidermis from various commercially available spray preparations was significantly lower than that of DEET from similar spray products, both alone and in combination with sunscreen oxybenzone. Concurrent application of the commercial products resulted in either no change or suppression of permeation of picaridin and oxybenzone. This finding was also different from concurrent application of DEET and oxybenzone using commercial preparations. In addition, permeation of picaridin and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type.It was concluded from this thesis that picaridin would be a better candidate for concurrent application with sunscreen preparations in terms of percutaneous permeation.

In this thesis, a series of in vitro diffusion studies were performed to evaluate the transmembrane permeation of picaridin and oxybenzone across human epidermis and poly(dimethylsiloxane) (PDMS) membrane. Transdermal permeation of picaridin and oxybenzone from four commercially available repellent and sunscreen products was also investigated by using different application concentrations and sequences. The results obtained were then compared to those of the repellent DEET and the sunscreen oxybenzone under identical experimental conditions. Permeation of picaridin and oxybenzone across human epidermis was suppressed when both compounds were used concurrently. Increasing concentration of the test compounds further reduced the permeation percentage of picaridin and oxybenzone. While permeation characteristics were correlative between human epidermis and artificial PDMS membrane, permeability of PDMS membrane was significantly larger than that of human epidermis. This finding was different from concurrent use of DEET and oxybenzone in which a synergistic permeation enhancement was observed between the two substances. Transdermal permeation of picaridin across human epidermis from various commercially available spray preparations was significantly lower than that of DEET from similar spray products, both alone and in combination with sunscreen oxybenzone. Concurrent application of the commercial products resulted in either no change or suppression of permeation of picaridin and oxybenzone. This finding was also different from concurrent application of DEET and oxybenzone using commercial preparations. In addition, permeation of picaridin and oxybenzone across human epidermis was dependent on application concentration, use sequence, and preparation type.It was concluded from this thesis that picaridin would be a better candidate for concurrent application with sunscreen preparations in terms of percutaneous permeation.

No description available.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone are commonly incorporated into commercially available repellent and sunscreen preparations. Both compounds have demonstrated an increased percutaneous permeation and systemic disposition after concurrent application in vitro and in vivo. The permeation enhancement between DEET and oxybenzone not only compromises their respective protective efficacy against biting insects and UV radiation, but also potentiates toxicological properties in susceptible subjects. The pharmacokinetic and toxicological profiles from concurrent use of DEET and oxybenzone were evaluated and compared in this thesis. DEET and oxybenzone were administered by intravenous and topical routes in rats, either alone and/or in combination, to compare the pharmacokinetics of parent compounds and their primary metabolites in vivo. To evaluate toxicological characteristics, rat primary cortical neurons and astrocytes, and rat hepatoma 1548 cells were exposed to DEET, oxybenzone and their metabolites in vitro, and cell viability was analyzed. Various behavioral testing protocols were also performed to assess arousal, locomotion, habituation, and motor coordination of rats over a 30-day study period. Concurrent topical application of DEET and oxybenzone enhanced the disposition of DEET and its metabolites in rats, but did not consistently affect the distribution of oxybenzone and its metabolites. The disappearance of DEET from skin application site was accelerated; its apparent elimination half-life was decreased while its plasma and tissue concentrations were predominantly increased. Cellular toxicity occurred at 1 μg/ml for neurons and 7-day exposure for both astrocytes and neurons. Viability of hepatoma cells was also reduced when treated with DEET, oxybenzone and their metabolites, either alone or in combination, most notably after 72 hours of exposure. However, no overt signs of toxicity were observed from behavioral testing in rats after a 30-day topical study. The pharmacokinetic data obtained was beneficial in understanding and elucidating absorption and biodistribution of DEET and oxybenzone in vivo. The toxicological data suggested that the risk for increasing adverse effects from concurrent skin application of repellents and sunscreens would be low and marginal in healthy individuals. Nevertheless, further studies should be carried out to assess the long-term health impact of these compounds in susceptible subjects, especially at higher application doses.

Ultraviolet filters are active ingredients in sunscreen that protect us from harmful UV radiation. However, organic UV filters are thought to have adverse effects on the environment and humans. In recent years, fear of harmful impacts of sunscreen has caused a surge of coral reef safe sunscreens to hit the market. These sunscreens, which contain inorganic metal oxides as UV filters, have been accepted as safe for humans and the environment until recently. Metal oxides in reef safe sunscreens may form intermediates in the water that can harm marine life and can absorb through the skin and into the blood, possibly disrupting normal bodily function. In this study, a 48-hour bioassay was run with Artemia salina and various UV filters at different concentrations to determine at what levels of exposure and to which UV filters the organism is sensitive. Three trials were run with one organism in each of the 200 bioassay wells and 20 replicates per treatment. At each data collection time, organism survival outcomes were recorded. Results showed significant difference between trials but not between treatments. This project serves to research the impact sunscreen has on A. salina and potential environmental and human health impacts.

No description available.

Clay minerals have historically played a consequential role in human health. While the beginnings were rooted in geophagy, a primitive act of consuming earth, the health-related uses of clay minerals have evolved and diversified over time. As excipients in pharmaceutical formulations, clay minerals can attribute novel properties onto intercalated compounds. Intercalating oxybenzone, a UV filter, within the interlamellar space of montmorillonite is desirable in order to minimize direct contact with skin. Intercalating resveratrol, a compound known for attributing beneficial effects onto human health, may be advantageous since this compound is susceptible to cis-trans isomerisation. The strategy of using alkylammonium–modified clay was undertaken and proved successful for the intercalation of oxybenzone. The field of biopolymer/layered silicate nanocomposites is heavily researched for use in a multitude of applications. Novel montmorillonite nanocomposites were prepared with neutral guar gum and cationic guar gum, using an environmentally friendly process and are fully characterized.