Regional variation in percutaneous absorption in the tree frog Litoria caerulea

Llewelyn, Victoria K.; Berger, Lee; Glass, Beverley

doi:10.1016/j.etap.2018.03.019

Cited by 6 publications

(20 citation statements)

References 26 publications

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“…Skin morphology in these species differs substantially, with X. laevis demonstrating a thicker skin overall with reduced vascularization across the entire body (Roth ) and L. caerulea having a relatively thick dorsum compared to its thin and highly vascularized ventral skin (personal observation). Absorption rates reported in these studies reflected these physiological differences in skin structure, with significantly higher flux of all chemicals through the ventral skin compared with the dorsum in L. caerulea (Llewelyn et al ). A slight increase in ventral flux was also reported in X. laevis (Kaufmann and Dohmen ); however, the magnitude of the difference was far less than that reported in L. caerulea , being no more than a 2.3‐fold increase for testosterone, compared to a 33‐fold increase between regions seen for ventral versus dorsal flux of caffeine in L. caerulea (Llewelyn et al ).…”

Section: Introductionmentioning

confidence: 66%

“…Postrun analysis was performed using LabSolutions 5.82 (Shimadzu). All HPLC methods used have been previously described and validated (Llewelyn et al ; summarized in Table ). All samples were run in triplicate.…”

Section: Methodsmentioning

confidence: 99%

“…The methodology utilized in determining the cutaneous absorption kinetics in the present study has been described (Llewelyn et al ). Briefly, 3 model chemicals—caffeine, benzoic acid, and ibuprofen—chemicals of similar molecular size (caffeine = 194.22 Da, benzoic acid = 122.13 Da, and ibuprofen = 206.28 Da) but differing relative lipophilicities (log P caffeine = –0.07, benzoic acid = 1.87, and ibuprofen = 3.97), were used.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Two recent studies (Kaufmann and Dohmen ; Llewelyn et al ) investigated the in vitro transdermal kinetics of various standard chemicals in isolated frog skin using static diffusion cells. Each study investigated a species from a different habitat: Kaufmann and Dohmen () conducted investigations in the aquatic frog Xenopus laevis , whereas Llewelyn et al () used the arboreal frog Litoria caerulea . Skin morphology in these species differs substantially, with X. laevis demonstrating a thicker skin overall with reduced vascularization across the entire body (Roth ) and L. caerulea having a relatively thick dorsum compared to its thin and highly vascularized ventral skin (personal observation).…”

Section: Introductionmentioning

confidence: 99%

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Effects of skin region and relative lipophilicity on percutaneous absorption in the toad Rhinella marina

Llewelyn

Berger

Glass

2018

Enviro Toxic and Chemistry

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Owing to the dynamic interaction between frog skin and the environment, xenobiotics in frog habitats are of particular concern, and knowledge of percutaneous absorption in frog skin is necessary for risk-mitigation purposes. Baseline transdermal kinetics in adult aquatic and arboreal frog species have recently been reported; however, there is little information regarding absorption kinetics in adult terrestrial species. The present study investigated the in vitro absorption kinetics of 3 model chemicals-caffeine, benzoic acid, and ibuprofen-through different skin regions in the terrestrial toad Rhinella marina. Caffeine flux was consistently higher than that of the other 2 chemicals (p < 0.001), whereas the fluxes of the moderately and highly lipophilic chemicals (benzoic acid and ibuprofen) were similar, regardless of skin region. When considering individual chemicals, caffeine demonstrated increased flux through the ventral pelvic skin compared with the ventral thoracic or dorsal skin regions. Flux did not differ between skin regions for either benzoic acid or ibuprofen. These findings have implications for management of environmental contamination in frog habitats, as many environmental xenobiotics are of moderate to high lipophilicity and would be expected to be equally absorbed from all skin surfaces in terrestrial toads. Environ Toxicol Chem 2019;38:361-367. C 2018 SETAC

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Section: Introductionmentioning

confidence: 66%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of skin region and relative lipophilicity on percutaneous absorption in the toad Rhinella marina

Llewelyn

Berger

Glass

2018

Enviro Toxic and Chemistry

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Permeability of frog skin to chemicals: effect of penetration enhancers

Llewelyn

Berger

Glass

2019

Heliyon

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Rarely do commercial chemical products contain solely the active chemical/ingredient. It is therefore important to consider whether ingredients other than the active may: 1) alter absorption of the active chemical, or 2) be absorbed themselves, resulting in systemic effects. Frogs have highly permeable skin and are routinely exposed to commercial chemical products in the environment or therapeutically. Ethanol and propylene glycol (PG), which have known penetration-enhancing effects, are commonly included in such products. The current study has therefore investigated the in vitro absorption kinetics through Rh. marina skin of three model chemicalscaffeine, benzoic acid, and ibuprofenformulated individually as solutions containing: 1%, 10% or 30% v/v ethanol, or 20% v/v PG. Differential scanning calorimetry and histology were used to characterise fresh frog skin, investigate the mechanism of these enhancers in frog skin, and to determine whether these enhancers significantly affected skin structure. Results showed that the extent of absorption enhancement was influenced by chemical, enhancer and skin region, and that enhancement was generally not consistent for individual enhancers or skin regions. The exception was 1% v/v ethanol, which did not significantly alter flux across the skin for any of the chemicals evaluated. Caffeine absorption was not enhanced by any of the investigated penetration enhancers, and was in fact significantly reduced by 30% v/v ethanol and PG. Ethanol caused concentration-dependant changes in skin morphology and should be avoided in concentrations !10% v/v. PG, however, caused minimal changes to the skin and consistently improved absorption of benzoic acid and ibuprofen through all skin regions. Owing to the significant changes in skin structure following !10% v/v ethanol exposure, it is recommended to avoid its use in frogs. For enhancement of penetration of moderately-to-highly lipophilic chemicals, this study has identified 20% v/v PG should to be the enhancer of choice.

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