Pharmacokinetic and toxicological characterization of repellent DEET and sunscreen oxybenzone
| dc.contributor.author | Fediuk, Daryl James | |
| dc.contributor.examiningcommittee | Simons, Keith (Pharmacy) Namaka, Michael (Pharmacy) Parkinson, Fiona (Pharmacology and Therapeutics) Singh, Jagdish (North Dakota State University) | en_US |
| dc.contributor.supervisor | Gu, Xiaochen (Pharmacy) | en_US |
| dc.date.accessioned | 2012-07-20T18:35:34Z | |
| dc.date.available | 2012-07-20T18:35:34Z | |
| dc.date.issued | 2011-10 | en_US |
| dc.date.issued | 2010-12 | en_US |
| dc.degree.discipline | Pharmacy | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | 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. | en_US |
| dc.description.note | October 2012 | en_US |
| dc.identifier.citation | Fediuk DJ, Wang T, Chen Y, et al. Tissue disposition of the insect repellent DEET and the sunscreen oxybenzone following intravenous and topical administration in rats. Biopharm Drug Dispos. Oct 2011;32(7):369-379 | en_US |
| dc.identifier.citation | Fediuk DJ, Wang T, Raizman JE, Parkinson FE, Gu X. Tissue deposition of the insect repellent DEET and the sunscreen oxybenzone from repeated topical skin applications in rats. Int J Toxicol. Dec 2010;29(6):594-603 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/8112 | |
| dc.language.iso | eng | en_US |
| dc.publisher | John Wiley & Sons, Ltd. | en_US |
| dc.publisher | SAGE Publications Ltd./SAGE Publications, Inc. | en_US |
| dc.rights | open access | en_US |
| dc.subject | insect repellent | en_US |
| dc.subject | sunscreen | en_US |
| dc.subject | tissue disposition | en_US |
| dc.subject | intravenous and topical administration | en_US |
| dc.subject | cellular toxicity | en_US |
| dc.subject | behavioral testing | en_US |
| dc.subject | DEET | |
| dc.subject | oxybenzone | |
| dc.title | Pharmacokinetic and toxicological characterization of repellent DEET and sunscreen oxybenzone | en_US |
| dc.type | doctoral thesis | en_US |