@article{muhammad_riviere_2007, title={Dermal toxicity}, ISBN={["978-0-12-370467-2"]}, DOI={10.1016/b978-012370467-2/50113-9}, abstractNote={Knowledge of the basic structure of skin is necessary to understand the mechanisms of dermal absorption and toxicity of topically applied toxicants. Skin is an essential and dynamic organ. It is composed of three distinct layers: epidermis, dermis, and hypodermis. In addition to performing important functions including thermoregulation and preventing insensible water loss, it also has important metabolic, immunological, and neurosensory properties. However, the predominant function of skin is to protect the body against a variety of toxicological insults. Animals are relatively less protective against such insults as compared to humans because of a lack of clothing, inferior housing, and different social interactions. In most instances, the skin of animals directly contacts environmental, chemical, and other pollutant exposure without the benefit of manmade protection. Although the largest organ of the body can often face these insults to a certain threshold, animals exhibit symptoms of dermal toxicity when this limit is passed.}, journal={VETERINARY TOXICOLOGY: BASIC AND CLINICAL PRINCIPLES}, author={Muhammad, Faqir and Riviere, Jim E.}, year={2007}, pages={263–276} } @inbook{muhammad_riviere_2006, title={In vivo models}, ISBN={0415700361}, booktitle={Dermal absorption models in toxicology and pharmacology}, publisher={New York: Taylor and Francis / CRC Press}, author={Muhammad, F. and Riviere, J. E.}, year={2006}, pages={47–68} } @article{muhammad_monteiro-riviere_riviere_2005, title={Comparative in vivo toxicity of topical JP-8 jet fuel and its individual hydrocarbon components: Identification of tridecane and tetradecane as key constituents responsible for dermal irritation}, volume={33}, ISSN={["1533-1601"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000227438200007&KeyUID=WOS:000227438200007}, DOI={10.1080/01926230590908222}, abstractNote={ Despite widespread exposure to military jet fuels, there remains a knowledge gap concerning the actual toxic entities responsible for irritation observed after topical fuel exposure. The present studies with individual hydrocarbon (HC) constituents of JP-8 jet fuel shed light on this issue. To mimic occupational scenarios, JP-8, 8 aliphatic HC (nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane) and 6 aromatic HC (ethyl benzene, o-xylene, trimethyl benzene, cyclohexyl benzene, naphthalene, dimethyl naphthalene) soaked cotton fabrics were topically exposed to pigs for 1 day and with repeated daily exposures for 4 days. Erythema, epidermal thickness, and epidermal cell layers were quantitated. No erythema was noted in 1-day in vivo HC exposures but significant erythema was observed in 4-day tridecane, tetradecane, pentadecane, and JP-8 exposed sites. The aromatic HCs did not produce any macroscopic lesions in 1 or 4 days of in vivo exposures. Morphological observations revealed slight intercellular and intracellular epidermal edema in 4-day exposures with the aliphatic HCs. Epidermal thickness and number of cell layers significantly increased ( p < 0.05) in tridecane, tetradecane, pentadecane, and JP-8-treated sites. No significant differences were observed in the aromatic HC-exposed sites. Subcorneal microabscesses containing inflammatory cells were observed with most of the long-chain aliphatic HCs and JP-8 in 4-day exposures. Ultrastructural studies depicted that jet fuel HC-induced cleft formation within intercellular lipid lamellar bilayers of the stratum corneum. The degree of damage to the skin was proportional to the length of in vivo HC exposures. These data coupled with absorption and toxicity studies of jet fuel HC revealed that specific HCs (tridecane and tetradecane) might be the key constituents responsible for jet fuel-induced skin irritation. }, number={2}, journal={TOXICOLOGIC PATHOLOGY}, author={Muhammad, F and Monteiro-Riviere, NA and Riviere, JE}, year={2005}, pages={258–266} } @article{muhammad_monteiro-riviere_baynes_riviere_2005, title={Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents}, volume={68}, ISSN={["1087-2620"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000229475900004&KeyUID=WOS:000229475900004}, DOI={10.1080/15287390590925456}, abstractNote={The percutaneous absorption of topically applied jet fuel hydrocarbons (HC) through skin previously exposed to jet fuel has not been investigated, although this exposure scenario is the occupational norm. Pigs were exposed to JP-8 jet fuel-soaked cotton fabrics for 1 and 4 d with repeated daily exposures. Preexposed and unexposed skin was then dermatomed and placed in flow-through in vitro diffusion cells. Five cells with exposed skin and four cells with unexposed skin were dosed with a mixture of 14 different HC consisting of nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethyl benzene, o-xylene, trimethyl benzene (TMB), cyclohexyl benzene (CHB), naphthalene, and dimethyl naphthalene (DMN) in water + ethanol (50:50) as diluent. Another five cells containing only JP-8-exposed skin were dosed solely with diluent in order to determine the skin retention of jet fuel HC. The absorption parameters of flux, diffusivity, and permeability were calculated for the studied HC. The data indicated that there was a two-fold and four-fold increase in absorption of specific aromatic HC like ethyl benzene, o-xylene, and TMB through 1- and 4-dJP-8 preexposed skin, respectively. Similarly, dodecane and tridecane were absorbed more in 4-d than 1-dJP-8 preexposed skin experiments. The absorption of naphthalene and DMN was 1.5 times greater than the controls in both 1- and 4-d preexposures. CHB, naphthalene, and DMN had significant persistent skin retention in 4-d preexposures as compared to 1-d exposures that might leave skin capable of further absorption several days postexposure. The possible mechanism of an increase in HC absorption in fuel preexposed skin may be via lipid extraction from the stratum corneum as indicated by Fourier transform infrared (FTIR) spectroscopy. This study suggests that the preexposure of skin to jet fuel enhances the subsequent in vitro percutaneous absorption of HC, so single-dose absorption data for jet fuel HC from naive skin may not be optimal to predict the toxic potential for repeated exposures. For certain compounds, persistent absorption may occur days after the initial exposure. This work was supported by U.S. Air Force Office of Scientific Research, grant F49620-01-1-0080.}, number={9}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Muhammad, F and Monteiro-Riviere, NA and Baynes, RE and Riviere, JE}, year={2005}, month={May}, pages={719–737} } @article{muhammad_brooks_riviere_2004, title={Comparative mixture effects of JP-8(100) additives on the dermal absorption and disposition of jet fuel hydrocarbons in different membrane model systems}, volume={150}, ISSN={["1879-3169"]}, DOI={10.1016/j.toxlet.2004.02.012}, abstractNote={Jet fuel are complex mixtures of hydrocarbon fuel components and performance additives. Three different membrane systems, silastic, porcine skin and the isolated perfused porcine skin flap (IPPSF) were used to gain insight into the possible mechanism for additive interactions on hydrocarbon component absorption. Influence of JP-8(100) additives on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of hydrocarbon absorption, were evaluated using analysis of means (ANOM) and analysis of variance (ANOVA). This study indicated that the naphthalene absorption through silastic membrane was significantly different with JP-8 plus individual additives as compared to controls, i.e. JP-8 and JP-8(100). The porcine skin data indicated that neither individual nor combinations of additives affected naphthalene absorption. The third membrane system (IPPSF) showed that only MDA and BHT were important additives altering naphthalene absorption. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption. MDA significantly decreased dodecane absorption in skin flaps. All individual and combinations of two additives with JP-8 affected naphthalene and dodecane surface retention in silastic membrane. The IPPSF indicated that only 8Q405 is a significant modulator of surface retention for both marker hydrocarbons. The 8Q405 significantly reduced naphthalene contents in dosed silastic and skin indicating a direct interaction between additive and marker hydrocarbons. The MDA and BHT, which significantly retained naphthalene in the stratum corneum of porcine skin individually, led to a statistical decrease in its retention in the stratum corneum when in combination (MDA+BHT) suggesting a potential biological interaction. These observations demonstrate that the single membrane system may not be suitable for the final prediction of complex additive interactions in jet fuels. Rather a combination of different membrane systems may provide the insight to elucidate the possible mechanism for additive interactions. Finally, it is important to assess all components of a chemical mixture since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Muhammad, F and Brooks, JD and Riviere, JE}, year={2004}, month={May}, pages={351–365} } @article{muhammad_baynes_monteiro-riviere_xia_riviere_2004, title={Dose related absorption of JP-8 jet fuel hydrocarbons through porcine skin with quantitative structure permeability relationship analysis}, volume={14}, ISSN={["1537-6524"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000220690300003&KeyUID=WOS:000220690300003}, DOI={10.1080/15376520490429319}, abstractNote={The effects of dosage on the percutaneous absorption of jet fuel hydrocarbons is not clear, yet is essential for human risk assessment. The present study is an ongoing approach to assess the dose-related percutaneous absorption of a number of aliphatic and aromatic hydrocarbons. The first treatment (1X) was comprised of mixtures containing undecane (4.1%), dodecane (4.7%), tridecane (4.4%), tetradecane (3%), pentadecane (1.6%), naphthalene (1.1%), and dimethyl naphthalene (1.3% of jet fuels) in hexadecane solvent using porcine skin flow through diffusion cell. Other treatments (n = 4 cells) were 2X and 5X concentrations. Perfusate samples were analyzed with gas chromatography-flame ionization detector (GC-FID) using head space solid phase micro-extraction fiber technique. We have standardized the assay to have a good linear correlation for all the tested components in media standards. Absorption parameters including diffusivity, permeability, steady state flux, and percent dose absorbed were estimated for all the tested hydrocarbons. This approach provides a baseline to access component interactions among themselves and with the diluent (solvents). A quantitative structure permeability relationship (QSPR) model was derived to predict the permeability of unknown jet fuel hydrocarbons in this solvent system by using their physicochemical parameters. Our findings suggested a dose related increase in absorption for naphthalene and dimethyl naphthalene (DMN).}, number={3}, journal={TOXICOLOGY MECHANISMS AND METHODS}, author={Muhammad, F and Baynes, RE and Monteiro-Riviere, NA and Xia, XR and Riviere, JE}, year={2004}, pages={159–166} }