@article{chang_williams_dauterman_riviere_1994, title={PERCUTANEOUS-ABSORPTION, DERMATOPHARMACOKINETICS AND RELATED BIO-TRANSFORMATION STUDIES OF CARBARYL, LINDANE, MALATHION, AND PARATHION IN ISOLATED-PERFUSED PORCINE SKIN}, volume={91}, ISSN={["0300-483X"]}, DOI={10.1016/0300-483x(94)90014-0}, abstractNote={The percutaneous absorption of topically applied pesticides is a primary route for systemic exposure and potential toxicity. The isolated perfused porcine skin flap (IPPSF) is an in vitro model for studying percutaneous absorption of xenobiotics as well as cutaneous metabolism and toxicity in an anatomically intact viable skin preparation. In the present studies, percutaneous absorption of four different pesticides, carbaryl (C), lindane (L), malathion (M), and parathion (P), was assessed topically in an ethanol vehicle. A 4-compartment pharmacokinetic model was utilized to model their absorption profile. The order of absorption was C > P > L > M for the 8-h experimental period, but C > L > P > M for a model-extrapolated 6-day prediction. Metabolism of C and P was also assessed by high performance liquid chromatography (HPLC). The HPLC results indicate a significant first-pass effect for both pesticides after topical application, with parathion being metabolized to paraoxon and para-nitrophenol and carbaryl to naphthol. In addition, comparison of the metabolic data of P with previous results underscores the difference between non-recirculating and recirculating IPPSF systems in xenobiotic metabolism studies.}, number={3}, journal={TOXICOLOGY}, author={CHANG, SK and WILLIAMS, PL and DAUTERMAN, WC and RIVIERE, JE}, year={1994}, month={Aug}, pages={269–280} }
 @article{chang_dauterman_riviere_1994, title={Percutaneous Absorption of Parathion and Its Metabolites, Paraoxon and p-Nitrophenol, Administered Alone or in Combination: In Vitro Flow-Through Diffusion Cell Studies}, volume={48}, ISSN={0048-3575}, url={http://dx.doi.org/10.1006/pest.1994.1007}, DOI={10.1006/pest.1994.1007}, abstractNote={Abstract The percutaneous absorption of individual pesticides has been well studied. However, the absorption of a mixture of pesticides and decomposition products or metabolites has not received attention. The percutaneous absorption of parathion (PA) relative to its two metabolites, paraoxon (PO) and p -nitrophenol (PNP), was studied in vitro using weanling pig skin in a flow-through diffusion cell system. Concentrations of 4, 40, or 400 μg/cm 2 of PA, PO, PNP, PA + PO (1:1), PA + PNP (1:1), and PO + PNP (1:1) in ethanol were applied topically. Environmental conditions such as air and perfusate temperature (37°C), relative humidity (60%), and flow rate (4 ml/hr) were controlled, and Kreb′s-Ringer bicarbonate buffer with 4.5% bovine serum albumin media was used. The total absorption of PA, PO, and the mixed compounds increased as the dose increased, whereas the absorption efficiency (percentage of applied dose absorbed) decreased as the doses increased. For the most water-soluble metabolite, PNP, both total absorption and absorption efficiency increased as the dose increased. Except for the 4 μg/cm 2 dose, the individual compounds followed the absorption order of PNP > PO > PA. For the mixed compounds, the rate of absorption followed the order PO + PNP > PA + PNP > PA + PO for all three dose combinations. However, after HPLC analysis of the perfusate, the amount of absorption of each component (PA, PO, and PNP) in mixed compounds was significantly different ( p}, number={1}, journal={Pesticide Biochemistry and Physiology}, publisher={Elsevier BV}, author={Chang, S.K. and Dauterman, W.C. and Riviere, J.E.}, year={1994}, month={Jan}, pages={56–62} }
 @article{chang_brownie_riviere_1994, title={Percutaneous absorption of topical parathion through porcine skin: in vitro studies on the effect of environmental perturbations}, volume={17}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.1994.tb00274.x}, DOI={10.1111/j.1365-2885.1994.tb00274.x}, abstractNote={Topical use of pesticides in domestic animals such as swine is a common practice: however, the effect of environmental factors on the extent of absorption has not received attention. Since no single factor can exert its effects alone in the natural environment, the interaction of environmental factors on the percutaneous absorption of pesticides must be understood before potential toxicity of dermal absorption of pesticides can be effectively estimated. In the present studies, the effects of air temperature (Ta), perfusate temperature (Tp), perfusate flow (F) and relative humidity (%RH) on absorption of parathion were studied in vitro in porcine skin. Parathion absorption was determined by measuring radiolabel appearing in the perfusate over time. Three main environmental parameters were found to have a significant effect on parathion penetration. Increasing T, from 37'C to 42oC %RH from 60% to 90% or F from 4 ml/h to 8 ml/h each produced a significant increase in penetration. The following significantly positive two‐way interactions among test parameters were seen: T, x F and %RH x F at the 4 μg dose, % RH × F at the 40 μg dose and T, ×%RH, T, x F and %RH × F at the 400 μg dose. There were no three‐way interactions at any of the three doses tested. These results suggest that the factors tested are not independent variables and must be considered interactive when used in assessing pesticide percutaneous absorption.}, number={6}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Chang, S. K. and Brownie, C. and Riviere, J. E.}, year={1994}, month={Dec}, pages={434–439} }
 @article{chang_riviere_1993, title={EFFECT OF HUMIDITY AND OCCLUSION ON THE PERCUTANEOUS-ABSORPTION OF PARATHION INVITRO}, volume={10}, ISSN={["0724-8741"]}, DOI={10.1023/A:1018901903243}, number={1}, journal={PHARMACEUTICAL RESEARCH}, author={CHANG, SK and RIVIERE, JE}, year={1993}, month={Jan}, pages={152–155} }
 @article{heit_williams_jayes_chang_riviere_1993, title={TRANSDERMAL LONTOPHORETIC PEPTIDE DELIVERY - INVITRO AND INVIVO STUDIES WITH LUTEINIZING-HORMONE-RELEASING HORMONE}, volume={82}, ISSN={["1520-6017"]}, DOI={10.1002/jps.2600820304}, abstractNote={Protein and peptide drugs are not orally active. Their large molecular size and charged character make them poor candidates for passive transdermal delivery. With an applied electromotive force, these drugs can be forced through the skin to be absorbed by the systemic circulation. The present study investigates the transdermal iontophoretic delivery of a peptide hormone in an in vitro model system, the isolated perfused porcine skin flap, as well as in vivo. It is shown that with knowledge of the systemic disposition of the drug, transdermal fluxes can be utilized to accurately predict in vivo serum concentrations. It is also shown that the iontophoretically delivered hormone retains both its immunologic and biologic activity.}, number={3}, journal={JOURNAL OF PHARMACEUTICAL SCIENCES}, author={HEIT, MC and WILLIAMS, PL and JAYES, FL and CHANG, SK and RIVIERE, JE}, year={1993}, month={Mar}, pages={240–243} }
 @inbook{riviere_chang_1992, title={Transdermal penetration and metabolism of organophosphate insecticides}, ISBN={0121673456}, DOI={10.1016/b978-0-08-091726-9.50016-1}, booktitle={Organophosphates: chemistry, fate and effects}, publisher={New York: Academic Press}, author={Riviere, J. E. and Chang, S.}, year={1992}, pages={241–253} }
 @article{chang_riviere_1991, title={PERCUTANEOUS-ABSORPTION OF PARATHION INVITRO IN PORCINE SKIN - EFFECTS OF DOSE, TEMPERATURE, HUMIDITY, AND PERFUSATE COMPOSITION ON ABSORPTIVE FLUX}, volume={17}, ISSN={["0272-0590"]}, DOI={10.1016/0272-0590(91)90200-N}, abstractNote={The effect of environmental factors on the percutaneous absorption of parathion in excised porcine skin was assessed in a flow-through diffusion cell system by varying the temperature (T), relative humidity (%RH), perfusate flow rate (F), and composition (porcine serum) at three parathion doses (4, 40, and 400 micrograms/cm2) compared to standard conditions (air temperature = 37 degrees C, perfusate temperature = 37 degrees C, %RH = 60, flow rate = 4 ml/hr, and standard bovine serum albumin medium). Parathion absorption was assessed by monitoring total radiolabeled activity appearing in the perfusate over time. High relative humidity significantly increased parathion penetration, as did two elevated temperature conditions. The effects of flow rate and perfusate composition were variable and dose dependent. In the present studies, lower applied doses appeared to be more sensitive to changes in the environmental conditions studied. These results suggest that these parameters have independent and different degrees of effect on parathion percutaneous absorption. Experimental conditions should be strictly controlled and dose-response studies need to be conducted when evaluating transdermal studies. Finally, if similar effects occur in vivo, the risk assessment calculations on percutaneous absorption should take these parameters into consideration.}, number={3}, journal={FUNDAMENTAL AND APPLIED TOXICOLOGY}, author={CHANG, SK and RIVIERE, JE}, year={1991}, month={Oct}, pages={494–504} }