@article{baynes_brooks_budsaba_smith_riviere_2001, title={Mixture effects of JP-8 additives on the dermal disposition of jet fuel components}, volume={175}, ISSN={["1096-0333"]}, DOI={10.1006/taap.2001.9259}, abstractNote={Aliphatic and aromatic components in formulated jet fuels can cause occupational dermatitis. However, the influence of JP-8 performance additives (DIEGME, 8Q21, and Stadis450) on the dermal disposition of fuel components is not well understood. These additives are formulated with commercial Jet-A to form military JP-8 fuel. The purpose of this study is to assess the influence of these additives on the dermal disposition of marker aromatic and aliphatic components, naphthalene and dodecane, respectively. Porcine skin sections in an in vitro system were used to characterize chemical-biological interactions that modulate diffusion of jet fuel components and isolated perfused porcine skin flaps (IPPSFs) were used to evaluate diffusion in a viable skin model with an intact microvasculature. In these 5-h studies, Jet-A, Jet-A + DIEGME, Jet-A + 8Q21, and Jet-A + Stadis450, Jet-A + DIEGME + 8Q21, Jet-A + DIEGME + Stadis450, Jet-A + 8Q21 + Stadis450, and JP-8 mixtures were tested. In general, naphthalene absorption (0.76-2.39% dose) was greater than dodecane absorption (0.10-0.84% dose), while the IPPSFs alone demonstrated that dodecane absorption was significantly greater in JP-8 than in Jet-A. Synergistic interactions with 8Q21 + Stadis450 appear to enhance systemic absorption of either naphthalene or dodecane, while DIEGME + Stadis450 increased naphthalene (1.88% dose) and dodecane (2.02% dose) penetration into the skin and fat tissues of IPPSFs. These findings were supported by the fact that 8Q21 + Stadis450 significantly increased dodecane flux and permeability in porcine skin sections, but 8Q21 alone reduced marker diffusion in both membrane systems. Furthermore, dodecane is more likely than naphthalene to remain in the stratum corneum and skin surface at 5 h, and DIEGME mixtures played a significant role in skin and surface retention of both markers. In summary, the data suggest that various combinations of these three performance additives in JP-8 can potentially alter the dermal disposition of aromatic and aliphatic fuel components in skin. More importantly, products of two-factor interactions were not predictable from single-factor exposures and, by extension, cannot be extrapolated to three-factor interactions.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Baynes, RE and Brooks, JD and Budsaba, K and Smith, CE and Riviere, JE}, year={2001}, month={Sep}, pages={269–281} } @article{riviere_smith_budsaba_brooks_olajos_salem_monteiro-riviere_2001, title={Use of methyl salicylate as a simulant to predict the percutaneous absorption of sulfur mustard}, volume={21}, ISSN={["1099-1263"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000167916500002&KeyUID=WOS:000167916500002}, DOI={10.1002/jat.718}, abstractNote={AbstractExposure to chemical vesicants such as sulfur mustard (HD) continues to be a threat to military forces requiring protectant strategies to exposure to be evaluated. Methyl salicylate (MS) has historically been the simulant of choice to assess HD exposure. The purpose of this study was to compare the percutaneous absorption and skin deposition of MS to HD in the isolated perfused porcine skin flap (IPPSF). The HD data were obtained from a previously published study in this model wherein 400 μg cm−2 of ]14C[‐MS or ]14C[‐HD in ethanol were topically applied to 16 IPPSFs and experiments were terminated at 2, 4 or 8 h. Perfusate was collected at increasing time intervals throughout perfusion. Radioactivity was determined in perfusate and skin samples. Perfusate flux profiles were fitted to a bi‐exponential model Y(t) = A(e− − e−) and the area under the curve (AUC), peak flux and time to peak flux were determined. Sulfur mustard had more pronounced and rapid initial flux parameters (P < 0.05). The AUCs determined from observed and model‐predicted parameters were not statistically different, although the mean HD AUC was 40–50% greater than MS. The HD skin and fat levels were up to twice those seen with MS, but had lower stratum corneum and residual skin surface concentrations (P < 0.05). Compared with other chemicals studied in this model, HD and MS cutaneous disposition were very similar, supporting the use of MS as a dermal simulant for HD exposure. Copyright © 2001 John Wiley & Sons, Ltd.}, number={2}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Riviere, JE and Smith, CE and Budsaba, K and Brooks, JD and Olajos, EJ and Salem, H and Monteiro-Riviere, NA}, year={2001}, pages={91–99} } @article{budsaba_smith_riviere_2000, title={Compass plots: A combination of star plot and analysis of means to visualize significant interactions in complex toxicology studies}, volume={10}, ISSN={["1051-7235"]}, DOI={10.1080/105172300750048764}, abstractNote={The Compass Plot, a new graphical methodthat combines the advantages of the star plot andthe analysis of means (ANOM), has beenintroducedfordisplaying the results of experiments. Incontrast to the star plot, this plot allows statistical inferences to be made for treatment and for factor effects. In contrast to ANOM, this plot is good for comparison in multiresponse experiments, a scenario becoming more commonplace in toxicology with the advent of increasing numbers of chemical mixture studies. An example of a 2 3 factorial chemical exposure experiment is considered here.}, number={4}, journal={TOXICOLOGY METHODS}, author={Budsaba, K and Smith, CE and Riviere, JE}, year={2000}, pages={313–332} } @article{riviere_brooks_monteiro-riviere_budsaba_smith_1999, title={Dermal Absorption and Distribution of Topically Dosed Jet Fuels Jet-A, JP-8, and JP-8(100)}, volume={160}, ISSN={0041-008X}, url={http://dx.doi.org/10.1006/taap.1999.8744}, DOI={10.1006/taap.1999.8744}, abstractNote={Dermal exposure to jet fuels has received increased attention with the recent release of newer fuels with novel performance additives. The purpose of these studies was to assess the percutaneous absorption and cutaneous disposition of topically applied (25 microl/5 cm(2)) neat Jet-A, JP-8, and JP-8(100) jet fuels by monitoring the absorptive flux of the marker components 14C naphthalene and (3)H dodecane simultaneously applied nonoccluded to isolated perfused porcine skin flaps (IPPSF) (n = 4). Absorption of 14C hexadecane was estimated from JP-8 fuel. Absorption and disposition of naphthalene and dodecane were also monitored using a nonvolatile JP-8 fraction reflecting exposure to residual fuel that might occur 24 h after a jet fuel spill. In all studies, perfusate, stratum corneum, and skin concentrations were measured over 5 h. Naphthalene absorption had a clear peak absorptive flux at less than 1 h, while dodecane and hexadecane had prolonged, albeit significantly lower, absorption flux profiles. Within JP-8, the rank order of absorption for all marker components was (mean +/- SEM % dose) naphthalene (1.17 +/- 0.07) > dodecane (0.63 +/- 0.04) > hexadecane (0.18 +/- 0.08). In contrast, deposition within dosed skin showed the reverse pattern. Naphthalene absorption into perfusate was similar across all fuel types, however total penetration into and through skin was highest with JP-8(100). Dodecane absorption and total penetration was greatest from JP-8. Absorption of both markers from aged JP-8 was lower than other fuels, yet the ratio of skin deposition to absorption was greatest for this treatment group. In most exposure scenarios, absorption into perfusate did not directly correlate to residual skin concentrations. These studies demonstrated different absorption profiles for the three marker compounds, differential effects of jet fuel types on naphthalene and dodecane absorption, and uncoupling of perfusate absorption from skin disposition.}, number={1}, journal={Toxicology and Applied Pharmacology}, publisher={Elsevier BV}, author={Riviere, Jim E. and Brooks, James D. and Monteiro-Riviere, Nancy A. and Budsaba, Kamon and Smith, Charles E.}, year={1999}, month={Oct}, pages={60–75} }