In vivo and ex vivo percutaneous absorption of [14C]-bisphenol A in rats: a possible extrapolation to human absorption?

Bisphenol A (BPA) is a monomer used mainly in the synthesis of polycarbonates and epoxy resins. Percutaneous absorption is the second source of exposure, after inhalation, in the work environment. However, studies on this route of absorption are lacking or incomplete. In this study, percutaneous BPA absorption was measured in vivo and ex vivo in the rat, and ex vivo in humans. An approximately 12-fold difference in permeability between rat skin and human skin was found, with permeability being higher in the rat. In addition, inter- and intra-individual variability of up to tenfold was observed in humans. No accumulation of BPA in the skin was found during exposure. The skin clearance rate following exposure was estimated at 0.4 μg/cm²/h. Ex vivo and in vivo percutaneous absorption fluxes of BPA in the rat were in the same range (about 2.0 μg/cm²/h), suggesting that extrapolation to the in vivo situation in humans may be possible. The European tolerable daily intake (TDI) of BPA is 50 μg/kg body weight. However, many research projects have highlighted the significant effects of BPA in rodents at doses lower than 10 μg/kg/day. A 1-h occupational exposure over 2,000 cm² (forearms and hands) may lead to a BPA absorption of 4 μg/kg/day. This is 8% of the European TDI and is very close to the value at which effects have been observed in animals. This absorption must therefore be taken into account when evaluating risks of BPA exposure, at least until more relevant results on the toxicity of BPA in humans are available

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Brevetoxins: Toxicological Profile

Brevetoxins (PbTxs) are polyether ladder-shaped neurotoxins produced by the dinoflagellate Karenia brevis. Blooms of K. brevis have been recorded since the mid-1800s, principally in the Gulf of Mexico but occasionally along the mid and south Atlantic coasts. Blooms may be accompanied by public health issues as well as significant mortalities of marine mammals, such as bottlenose dolphins and manatees, fishes, sea birds, and sea turtles. PbTxs bind to the voltage-gated sodium channels (VGSCs), leading to persistent activation of neuronal, muscle, and cardiac cells. In humans, after consumption of contaminated shellfish (oysters, clams, whelks), these toxins cause a syndrome known as neurotoxic shellfish poisoning (NSP), characterized by nausea, diarrhea, vomiting, abdominal pain, paresthesia, myalgia, ataxia, bradycardia, loss of coordination, vertigo, and mydriasis. The ingestion of contaminated seafood represents the most dangerous route of exposure for humans. However, when PbTxs are aerosolized through the disruption of K. brevis cells by breaking waves or winds, people can suffer from respiratory effects such as conjunctivitis, rhinorrhea, and bronchoconstriction. Due to successful shellfish monitoring programs managed by the Gulf coast states, cases of human intoxications are fortunately rather rare, and no human fatalities have been attributed to NSP