Metabolic Disposition of the Insect Repellent DEET and the Sunscreen Oxybenzone Following Intravenous and Skin Administration in Rats

Abstract

Insect repellent N,N-diethyl-m-toluamide (DEET) and sunscreen oxybenzone have shown a synergistic percutaneous enhancement when applied concurrently. Both compounds are extensively metabolized in vivo into a series of potentially toxic metabolites: 2 metabolites of DEET, N,N-diethyl-m-hydroxymethylbenzamide (DHMB) and N-ethyl-m-toluamide (ET), and 3 metabolites of oxybenzone, 2,4-dihydroxybenzophenone (DHB), 2,2-dihydroxy-4-methoxybenzophenone (DMB), and 2,3,4-trihydroxybenzophenone (THB). In this study, the metabolites were extensively distributed following intravenous and topical skin administration of DEET and oxybenzone in rats. Combined application enhanced the disposition of all DEET metabolites in the liver but did not consistently affect the distribution of oxybenzone metabolites. The DHMB appeared to be the major metabolite for DEET, while THB and its precursor DHB were the main metabolites for oxybenzone. Repeated once-daily topical application for 30 days led to higher concentrations of DEET metabolites in the liver. Hepatoma cell studies revealed a decrease in cellular proliferation from all metabolites as single and combined treatments, most notably at 72 hours. Increased accumulation of DHMB and ET in the liver together with an ability to reduce cellular proliferation at achievable plasma concentrations indicated that simultaneous exposure to DEET and oxybenzone might have the potential to precipitate adverse effects in a rat animal model.

Mild Effects of Sunscreen Agents on a Marine Flatfish: Oxidative Stress, Energetic Profiles, Neurotoxicity and Behaviour in Response to Titanium Dioxide Nanoparticles and Oxybenzone

“…Regarding BP-3 metabolism and excretion, no information is available for fish and the majority of the data are for rats. Contrary to TiO 2 NPs, high amounts of BP-3 and its metabolites are found in the kidney [66,67], suggesting excretion through this organ. Nevertheless, in the present study, the kidney's role in the excretion of BP-3 cannot be confirmed.…”

In vitro blastocyst implantation and trophoblast migration are disrupted by the UV filter benzophenone-3 (BP3)

“…One of the most widely used dermal PCPs are sunscreen products, which have become an integral part of summer routine for the general population, mainly due to a growing awareness of the risks derived from exposure to the sun. Benzophenone-3 (BP3) or oxybenzone is one of the main substances used as an active ingredient in sunscreens, due to its wellestablished UV-blocking e cacy (Emonet et al 2001;Fediuk et al 2012). BP3 shows clear estrogenic and antiandrogenic effects in vitro, although anti-progesterone and thyroid actions cannot be excluded (Mustieles et al 2023;Schlumpf et al 2001).…”

In vivo Visualization of Collagen Transdermal Absorption by Second-Harmonic Generation and Two-Photon Excited Fluorescence Microscopy

“…To date, various technologies have been applied to measure the biomedical administration of collagen to skin, including chemical assays (Fediuk et al, 2012), tissue inspection (Schulz et al, 2002), isotope tracing (Cross et al, 2007) and circulating diffusion chamber (Gamer et al, 2006), which can only be used to quantitatively examine the transdermal absorption of exogenous collagen in vitro. However, these approaches could not dynamically track the process of transdermal absorption in vivo and evaluate the real-time effects of biomedical administration.…”