Dermal Uptake is an Important Pathway for the Bioconcentration of Hydrophobic Organic Compounds by Zebrafish (Danio rerio).

For bioconcentration of hydrophobic organic compounds (HOCs), most of studies assumed that fish absorb HOCs mainly through gills but often ignored the dermal uptake. In this study, deuterated polycyclic aromatic hydrocarbons (PAHs-d10, phenanthrene-d10, and pyrene-d10) and polychlorinated biphenyls (PCB-153) were selected to study whether zebrafish can absorb freely dissolved and dissolved organic matter (DOM)-associated HOCs through dermal uptake. The results showed that the freely dissolved PAHs and PCBs could directly enter the body of zebrafish through its skin. However, PAHs and PCB-153 associated with DOM (~ 10 kDa) could not enter zebrafish through the skin. When gill and dermal exposure coexisted, dermal uptake contributed 2.9 ~ 7.6% and 31.9 ~ 38.4% of PAHs and PCB-153 bioconcentration after exposure for 6 h, respectively. The present study demonstrates that dermal uptake is an important pathway for the bioconcentration of HOCs by fish, which should be considered when studying the toxicodynamics and toxicokinetics of HOCs in organisms.

Indoor phthalate exposure and contributions to total intake among pregnant women in the SELMA study.

Phthalates are widely used in consumer products. Exposure to phthalates can lead to adverse health effects in humans, with early-life exposure being of particular concern. Phthalate exposure occurs mainly through ingestion, inhalation, and dermal absorption. However, our understanding of the relative importance of different exposure routes is incomplete. This study estimated the intake of five phthalates from the residential indoor environment for 455 Swedish pregnant women in the SELMA study using phthalate mass fraction in indoor dust and compares these to total daily phthalate intakes back-calculated from phthalate metabolite concentrations in the women's urine. Steady-state models were used to estimate indoor air phthalate concentrations from dust measurements. Intakes from residential dust and air made meaningful contributions to total daily intakes of more volatile di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), and di-iso-butyl phthalate (DiBP) (11% of total DEP intake and 28% of total DnBP and DiBP intake combined). Dermal absorption from air was the dominant pathway contributing to the indoor environmental exposure. Residential exposure to less volatile phthalates made minor contributions to total intake. These results suggest that reducing the presence of low molecular weight phthalates in the residential indoor environment can meaningfully reduce phthalate intake among pregnant women.

A review of the success and challenges in characterizing human dermal exposure to flame retardants.

Since organic flame retardants (FRs) have several industrial applications, they have been largely detected in environmental and biological samples, and humans have been highly exposed to them. Although the effects of oral and inhaled FRs have been well studied, dermal exposure to them has only recently been pointed out as a potential route of human exposure. Consequently, the effects of FRs on the skin and secondary target organs have been poorly investigated. This review article summarizes the main findings regarding dermal exposure to FRs, points the limitation of the published studies, and suggests future perspectives for better understanding of how dermal exposure to FRs impacts the human health. This review lists some gaps that must be filled in future studies, including characterization of the bioavailable fraction and assessment of exposure for new FRs, to establish their physiological significance and to improve the development of 3D dermal tissue for more reliable results to be obtained.

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects.

To better understand the dermal exposure pathway, we enhance an existing mechanistic model of transdermal uptake by including skin surface lipids (SSL) and consider the impact of clothing. Addition of SSL increases the overall resistance to uptake of SVOCs from air but also allows for rapid transfer of SVOCs to sinks like clothing or clean air. We test the model by simulating di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) exposures of six bare-skinned (Weschler et al. 2015, Environ. Health Perspect., 123, 928) and one clothed participant (Morrison et al. 2016, J. Expo. Sci. Environ. Epidemiol., 26, 113). The model predicts total uptake values that are consistent with the measured values. For bare-skinned participants, the model predicts a normalized mass uptake of DEP of 3.1 (µg/m2 )/(µg/m3 ), whereas the experimental results range from 1.0 to 4.3 (µg/m2 )/(µg/m3 ); uptake of DnBP is somewhat overpredicted: 4.6 (µg/m2 )/(µg/m3 ) vs. the experimental range of 0.5-3.2 (µg/m2 )/(µg/m3 ). For the clothed participant, the model predicts higher than observed uptake for both species. Uncertainty in model inputs, including convective mass transfer coefficients, partition coefficients, and diffusion coefficients, could account for overpredictions. Simulations that include transfer of skin oil to clothing improve model predictions. A dynamic model that includes SSL is more sensitive to changes that impact external mass transfer such as putting on and removing clothes and bathing.

Effect of Skin Protection and Skin Irritation on the Internal Exposure to Carbon Disulfide in Employees of the Viscose Industry.

INTRODUCTION: Occupational exposure to carbon disulfide (CS2) leads to inhalative and dermal uptake and thereby to internal exposure. In order to prevent occupational contact dermatitis, gloves and skin protection creams are used at the workplace. The aim of the study was the evaluation of the influence of personal skin protection and irritation on the internal exposure to CS2 of employees in the viscose industry. METHODS: One hundred and eighty-two male CS2-exposed employees were included in the study and were examined regarding working conditions, use of personal protective measures und skin status. Personal air monitoring and biological monitoring was performed and the 'relative internal exposure' (RIE, internal exposure in relation to external exposure) calculated. A multiple regression analysis calculated the influence of skin protection and irritation on CS2 uptake. RESULTS: Usage of skin protection creams and gloves (and both in combination) while working was associated with a significantly higher RIE indicating a higher dermal penetration of CS2. Equally, irritated skin and younger age was associated with a higher internal burden. CONCLUSIONS: Gloves and skin protection creams are useful for preventing occupational skin diseases. However, when handling skin-resorptive substances like CS2, they can increase internal exposure or skin irritation. Therefore, we recommend the careful consideration of benefits and risks of protective creams and gloves at the workplace.

Methods for the characterisation of dermal uptake: Progress and perspectives for organophosphate esters.

Organophosphate esters (OPEs) are a group of pollutants that are widely detected in the environment at high concentrations. They can adversely affect human health through multiple routes of exposure, including dermal uptake. Although attention has been paid to achieving an accurate and complete quantification of the dermal uptake of OPEs, existing evaluation methods and parameters have obvious weaknesses. This study reviewed two main categories of methodologies, namely the relative absorption (RA) model and the permeability coefficient (PC) model, which are widely used to assess the dermal uptake of OPEs. Although the PC model is more accurate and is increasingly used, the most important parameter in this model, the permeability coefficient (Kp), has been poorly characterised for OPEs, resulting in considerable errors in the estimation of the dermal uptake of OPEs. Thus, the detailed in vitro methods for the determination of Kp are summarised and sorted. Furthermore, the commonly used skin membranes are identified and the factors affecting Kp and corresponding mechanisms are discussed. In addition, the experimental conditions, conclusions, and available data on Kp values of the OPEs are thoroughly summarised. Finally, the corresponding knowledge gaps are proposed, and a more accurate and sophisticated experimental system and unknown Kp values for OPEs are suggested.

Inhalation and dermal absorption as dominant pathways of PCB exposure for residents of contaminated apartment buildings.

Applications of polychlorinated biphenyls (PCBs) in buildings and their persistence in indoor environments have led to cases of current and highly elevated exposure in humans, despite the global cease of production decades ago. Personal exposure to PCBs was assessed among residents in a social housing estate in Denmark containing both contaminated (n = 67) and non-contaminated (n = 23) apartments. Samples and estimated daily intakes (EDIs) were assessed for 15 PCB congeners, and body burden, which was limited by the dietary data availability, was compared across 7 indicator PCBs, with its sum (PCBsum7) often applied in European regulation of PCBs. Median PCBsum7 EDI across measured pathways for exposed residents was 101 ng· (kg bodyweight)-1· day-1, with the majority of exposure (60%) coming from inhalation of contaminated indoor air. Calculated from both PCBs measured in indoor air and on hand wipes, dermal absorption estimates showed comparable results and served as a secondary exposure pathway, accounting for 35% of personal exposure and considering selected assumptions and sources of physical-chemical parameters. Estimates revealed that diet was the primary PCB source among the reference group, accounting for over 75% of the PCBsum7 EDI across exposure routes. When evaluating overall EDIs across the two study groups and including dietary estimates, PCB exposure among exposed residents was around 10 times higher than the reference group. Solely within the exposed population, pathway-specific body burdens were calculated to account for exposure across years of residence in contaminated apartments, where lower chlorinated PCBs were dominant in indoor air. Among these dominant congeners, estimated body burdens of PCB-28 and -52 were significantly correlated with measured serum (rs = 0.49, 0.45; p < 0.001). This study demonstrates that inhalation and dermal absorption serve as dominant exposure pathways for residents of apartments contaminated with predominantly lower chlorinated PCBs and suggest that predictions of body burden from indoor environment measurements may be comparable to measured serum PCBs.

Exposure to oxybenzone from sunscreens: daily transdermal uptake estimation.

BACKGROUND: Fugacity, the driving force for transdermal uptake of chemicals, can be difficult to predict based only on the composition of complex, non-ideal mixtures such as personal care products. OBJECTIVE: Compare the predicted transdermal uptake of benzophenone-3 (BP-3) from sunscreen lotions, based on direct measurements of BP-3 fugacity in those products, to results of human subject experiments. METHODS: We measured fugacity relative to pure BP-3, for commercial sunscreens and laboratory mixtures, using a previously developed/solid-phase microextraction (SPME) method. The measured fugacity was combined with a transdermal uptake model to simulate urinary excretion rates of BP-3 resulting from sunscreen use. The model simulations were based on the reported conditions of four previously published human subject studies, accounting for area applied, time applied, showering and other factors. RESULTS: The fugacities of commercial lotions containing 3-6% w/w BP-3 were ~20% of the supercooled liquid vapor pressure. Simulated dermal uptake, based on these fugacities, are within a factor of 3 of the mean results reported from two human-subject studies. However, the model significantly underpredicts total excreted mass from two other human-subject studies. This discrepancy may be due to limitations in model inputs, such as fugacity of BP-3 in lotions used in those studies. SIGNIFICANCE: The results suggest that combining measured fugacity with such a model may provide order-of-magnitude accurate predictions of transdermal uptake of BP-3 from daily application of sunscreen products.

Characterization of chemical transport in human skin and building material.

Volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) are ubiquitous in indoor environment. They can emit from source into air, and subsequently penetrate human skin into blood through dermal uptake, causing adverse health effects. This study develops a two-layer analytical model to characterize the VOC/SVOC dermal uptake process, which is then extended to predict VOC emissions from two-layer building materials or furniture. Based on the model, the key transport parameters of chemicals in every skin or material layer are determined via a hybrid optimization method using data from experiments and literature. The measured key parameters of SVOCs for dermal uptake are more accurate than those from previous studies using empirical correlations. Moreover, the association between the absorption amount of studied chemicals into blood and age is preliminarily investigated. Further exposure analysis reveals that the contribution of dermal uptake to the total exposure can be comparable with that of inhalation for the examined SVOCs. This study makes the first attempt to accurately determine the key parameters of chemicals in skin, which is demonstrated to be critical for health risk assessment.

A critical review of human exposure to organophosphate esters with a focus on dietary intake.

Organophosphate esters (OPEs) are common additives in a wide range of commercial and industrial products. Elevated and prolonged exposure to OPEs may induce several adverse effects. This is concerning as they are ubiquitous in air, indoor dust, drinking water, and other environmental matrices. However, information on the presence of OPEs in foodstuffs and consequent health risks remains scant. This review critically evaluates available information on levels and sources of OPEs in food, discusses the relative significance of diet as a pathway of human exposure, identifies knowledge gaps, and suggests directions for future research. For toddlers, dermal uptake from dust ingestion appears the predominant pathway of exposure to chlorinated OPEs, as well as ethylhexyl diphenyl phosphate (EHDPP) and triphenyl phosphate (TPHP). In contrast, diet appears the main pathway of exposure to all eight OPEs considered for adults, and for tri n-butyl phosphate (TnBP), tris 2-ethylhexyl phosphate (TEHP), and tris (2-butoxyethyl) phosphate (TBOEP) for toddlers. While summed exposures via all pathways are within reference dose (RfD) values, they do not include high-end exposure estimates, and for highly-exposed individuals, the margin between exposure and RfD values is smaller. Moreover, our exposure estimates are based on a meta-analysis of multiple exposure assessments conducted over a range of points in space and time. There is an urgent need for assessments of human exposure to OPEs that examine all relevant pathways in a spatially and temporally-consistent fashion. Given food is an important exposure pathway to OPEs, regular monitoring of their presence as well as their metabolites (that may have toxicological significance) in foodstuffs is recommended. While dermal uptake from indoor dust appears an important human exposure pathway, no evaluations exist of exposure via dermal uptake from OPE-containing products such as foam-filled furniture. This review also highlights very few data exist on OPEs in drinking water.

Exposure to phthalates and correlations with phthalates in dust and air in South China homes.

We spend more than half of our daily time in indoor environments, and the contributions of phthalates present in it to total exposure are important. Here, we determined phthalate concentrations in paired indoor settled dust/air and their metabolites in human urine from 100 general families in south China to explore such kind of effect. The total concentrations of phthalates/metabolites were 48.7-2850 µg/g, 279-5080 ng/m3 and 10.7-2840 ng/mL in the indoor dust, air and urine samples, respectively. Among all targets, di-n-butyl phthalate, di-isobutyl phthalate and di-(2-ethylhexyl) phthalate and their metabolites were the predominant compounds. The daily intakes (DIs) of phthalates via dust or air decreased with age, except for infant, and the values of dust ingestion, air inhalation and air dermal uptake were 2720 ± 2460, 1300 ± 973 and 3590 ± 2890 ng/kg/day for toddlers and 236 ± 194, 360 ± 179 and 1120 ± 586 ng/kg/day for adults, respectively. The ratios of DIs from air to dust were greater than 1.0 for people in all age groups, and the ratio was the highest for adults. Furthermore, the contributions of phthalates from indoor dust and air to total DIs from all sources (estimated from urinary phthalate metabolites) were 0.60%-5.23% and 2.65%-12.2% for different ages, respectively. Our results indicated that indoor air was a quite important source for human exposure to phthalates in indoor environment in south China.

Characterization of phthalates in sink and source materials: Measurement methods and the impact on exposure assessment.

The fate and transport of semi-volatile organic compounds (SVOCs) in residential environments is significantly influenced by emission and sorption processes, which can be characterized by three key parameters: the gas-phase SVOC concentration adjacent to the material surface (y0); the diffusion coefficient (Dm); and the partition coefficient (K). Accurate determination of these three key parameters is critical for investigating SVOC mass transfer principles, and for assessing human health risks. Based on the mass transfer process of phthalates in a ventilated chamber, a novel method is developed to simultaneously measure Dm and K (key sorption parameters) in sink materials. The Dm and K of four target phthalates in a common T-shirt (sink material) are determined, and compared with those reported in literature. Results demonstrate that the measured parameters are in good agreement with those previously reported (relative deviation < 20 %), validating the effectiveness of proposed method. In addition, this method can be applied to determine y0, a key parameter from source materials. Results indicate that y0 determined with this method is consistent with that measured by literature method. Finally, dermal exposure analysis is performed, showing that dermal uptake of target phthalates is greatly affected by clothes.

Measuring exposure of e-waste dismantlers in Dhaka Bangladesh to organophosphate esters and halogenated flame retardants using silicone wristbands and T-shirts.

Silicone (polydimethylsiloxane or PDMS) wristbands and cotton T-shirts were used to assess the exposure of e-waste recyclers in Dhaka, Bangladesh to polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), dechlorane plus (DPs), and organophosphate esters (OPEs). The median surface-normalized uptake rates of PBDEs, NBFRs, DPs, and OPEs were 170, 8.5, 4.8, and 270 ng/dm2/h for wristbands and 5.4, 2.0, 0.94, and 23 ng/dm2/h for T-shirts, respectively. Concentrations of Tris(2-chloroethyl) phosphate (TCEP), Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), Tri-m-cresyl phosphate (TmCP), Bis(2-ethlyhexyl) tetrabromophthalate (BEH-TEBP), and Dechlorane plus (DPs) in wristbands were significantly correlated with those in T-shirts. Wristbands accumulated ~7 times more mass than T-shirts, especially of compounds expected to be mainly in the gas phase. We introduce the silicone "sandwich" method to approximate the easily releasable fraction (ERF) from T-shirts, hypothesized to be related to dermal exposure. ERFs varied from 6 to 75% of total chemical accumulated by T-shirts and were significantly negatively correlated with compounds' octanol-air partition coefficient (log Koa). The median daily exposure doses via dermal transfer from the front of the T-shirt to the front body trunk were 0.32, 0.13, 0.11, and 9.1 ng/kg-BW/day for PBDEs, NBFRs, DPs, and OPEs, respectively. The evidence of e-waste recycler exposure to flame retardants in this low income country, lacking protective personal equipment, calls for measures to minimize their exposure and for chemical management regulations to consider exposures to chemicals in waste products.

Dermal contact with furniture fabrics is a significant pathway of human exposure to brominated flame retardants.

Despite extensive application in consumer products and concerns over their adverse health effects, how external exposure to brominated flame retardants (BFRs) contributes to their human body burdens is not yet fully understood. While recent studies focused on inadvertent indoor dust ingestion and diet as potential major pathways of exposure, dermal uptake has been largely overlooked. We provide the first experimentally-based assessment of dermal uptake of BFRs via contact with indoor dust and flame-retarded furniture fabrics. Results reveal substantial uptake from furniture fabrics (e.g. 8.1 ng pentaBDE/kg bw/day for adults in summer), exceeding the overall adult intake of pentaBDE estimated previously via other exposure pathways. For HBCDs, despite the low absorption fraction (<2.5%) from the studied fabrics, the estimated dermal uptake of UK adults and toddlers (101 and 76.9 ng/kg bw/day) exceed the reported average daily intakes of 7.9 and 43.0 ng/kg bw/day for these UK age groups. Conversely, uptake from dust was low (0.05 and 0.19 ng pentaBDE/kg bw/day for adults and toddlers, respectively), indicating previous pharmacokinetic approaches may have overestimated the significance of this route. Future exposure and risk assessment studies should consider dermal contact with treated products as a significant pathway of human exposure to BFRs and related chemicals.

Estimation of intake and uptake of bisphenols and triclosan from personal care products by dermal contact.

Increasing concern has been raised in respect of exposure to bisphenols and triclosan (TCS) due to their widespread use. However, little is known about their occurrence in personal care products (PCPs) or, particularly, their dermal uptake following daily application. It is therefore necessary to evaluate the human health risk of bisphenols and TCS via dermal absorption. In this study, 150 PCPs, covering 11 different categories, were collected in China. The concentrations of seven bisphenol analogues and TCS were measured, and the associated human health risks by dermal contact were estimated. High detection frequencies of TCS (46.7%) and bisphenol AF (38.7%) were found in the PCPs. The highest mean concentration of Σ7BPs (sum concentration of all seven bisphenols) was 77.8ngg-1 found in masks, and the highest mean concentration of TCS was 86.7ngg-1 in hand sanitizers. The bisphenol composition profiles varied among different categories. Bisphenol A and bisphenol F generally showed higher concentrations. Combining the concentrations of the target substances with the daily usage quantities of PCPs and other parameters, the total estimated dermal intakes and uptakes of Σ7BPs and TCS were calculated. The results showed that the former (12.1 and 1.06ng·kg-1bwday-1) were markedly higher than the latter (1.21 and 9.58×10-2ng·kg-1bwday-1), which included dermal absorption rates of the chemicals in the estimation. Although diet is the main source, and oral ingestion is the main route, for human BPA exposure, the results of the estimated dermal uptakes of BPA in the present study combined with those from a European study show that dermal contact is the main route with thermal paper being the main contributor when both unconjugated and conjugated BPA in the human body are considered. The present study also showed that exposure to BPA in PCPs following dermal contact should not be ignored.

Benzophenone-UV filters in personal care products and urine of schoolchildren from Shenzhen, China: Exposure assessment and possible source.

The use of benzophenone (BP)-type UV filters in personal care products (PCPs) has rapidly increased in China over the past decade, leading to growing concerns on the potential adverse effects associated with the usage. Urine analysis is an ideal non-invasive approach for human biomonitoring of xenobiotics that are excreted mainly through urinary system. To investigate human exposure of PCPs to children from South China, we determined BP-type UV filters in a total of 156 commercial PCP goods covering 11 categories, as well as 280 urine samples collected from elementary school students in Shenzhen, China. Five BP analogues (i.e., BP1, BP2, BP3, BP8, and 4HB) were frequently detected in both PCPs and urine, among which BP3 was the dominant analogue, accounting for 96.3% of the total BPs in PCPs and 53.2% in urine, respectively. Sunscreens contained the highest BP concentrations (mean: 2.15 × 104 ng g-1) among all PCP goods. Girls exhibited higher urinary BP concentrations than boys, and body mass index positively influenced BP concentrations. However, no regional difference in urinary BP concentration was observed. The estimated dermal uptake of BPs from PCPs after considering the percutaneous absorption rates was much lower than the estimated dermal intake. The total daily excretion doses estimated from urinary BPs were 74.4 and 47.4 ng·kg-1bw day-1 for girls and boys, respectively. The higher usage of body lotions, hand lotions, and sunscreens by girls than boys (1.49 vs. 1.03 times week-1) might play an important role.

In vitro determination of transdermal permeation of synthetic musks and estimated dermal uptake through usage of personal care products.

Synthetic musks, chemical constituents of personal care products, enter the human body through dermal contact. Elucidation of the mechanisms underlying transdermal permeation of synthetic musks should enhance our understanding of their uptake and distribution in human skin and allow accurate evaluation of associated human exposure. Here, the transdermal permeation dynamics and distribution of galaxolide (HHCB) and tonalide (AHTN) were investigated using an in vitro skin diffusion model. The transdermal permeation amounts of HHCB and AHTN increased rapidly during the first 6 h. The applied HHCB and AHTN amounts did not affect percutaneous absorption rates. HHCB and AHTN remained primarily in the stratum corneum, accounting for 70.0% and 70.3% of the totals during the 24-h period, respectively. The percutaneous absorption rate of both chemicals was ∼11%. HHCB, AHTN, musk ketone, musk xylene, and Musk-T were detected in 29 personal care products. The average total concentrations of the musks were 3990, 54.0, 17.7, and 9.8 µg g-1 in perfume, shampoo, lotion, and shower gel, respectively. Among the four product categories, HHCB was dominant (57.4%-99.6%), followed by AHTN. The data clearly indicate that polycyclic and nitro musks are most commonly used in personal care products. The total estimated dermal intake (51.6 µg kg-1bw day-1) was markedly higher than total dermal uptake (5.9 µg kg-1bw day-1) when percutaneous absorption rates of the chemicals were added into the calculation. Uptake of HHCB and AHTN via dermal contact of personal care products was significantly higher than that from dust inhalation calculated according to earlier literature data.

Novel Drug Delivery System for Dermal Uptake of Etofenamate: Semisolid SLN Dispersion.

BACKGROUND: Semisolid SLNs are novel strategy for dermal drug administration instead of incorporating the SLN dispersions into conventional semisolids. Etofenamate loaded semisolid SLNs were successfully prepared and in vitro characterization of formulations were performed in our previous study. The present study is an attempt to evaluate the dermal behavior of the semisolid SLNs selected on the basis of previous research and investigate the properties in terms of the convenience for topical applications. OBJECTIVE: The objective of this study is to evaluate the skin penetration characteristics of semisolid SLN formulations. The occlusive and mechanical properties of semisolid SLNs were also evaluated because of their impression on the dermal behavior of the formulations. METHOD: The occlusive properties were investigated by in vitro occlusion test. Texture analysis was performed to define the hardness, compressibility, adhesiveness, cohesiveness and elasticity of the formulations. Rat skin was chosen to evaluate the ex vivo penetration of etofenamate loaded semisolid SLNs and commercial gel product. Coumarin-6 was used to visualize the dermal distribution of the semisolid SLN formulations. For monitorizing the penetration of coumarin-6 into the skin samples Confocal Laser Scanning Microscopy was employed. RESULTS: The occlusive and mechanical properties of C1 coded semisolid SLN formulation were found more favorable in comparison with P1. The cumulative etofenamate amount in skin samples was found to be 39.88 ± 1.50 µg/cm2 for C1 and 30.56 ± 2.10 µg/cm2 for P1 coded formulations. According to CLSM images, greater fluorescence intensities and deeper skin penetrations were obtained with both of the semisolid SLNs in comparison to plain Carbopol gel. CONCLUSION: It can be concluded that the semisolid SLNs are promising alternative dermal drug delivery systems to the conventional dosage forms.